Volume 6 Supplement 2
Detecting gene-gene interactions in prostate disease in African American men
© Reams et al; licensee BioMed Central Ltd. 2011
Published: 23 September 2011
The most common male malignancy in the United States is prostate cancer; however its rate of occurrence varies significantly among ethnic groups. In a previous cDNA microarray study on CaP tumors from African American (AA) and Caucasian (CA) patients, we identified 97 candidate genes that exhibited opposite gene expression polarity with respect to race groups; genes up-regulated in AA were simultaneously down-regulated in CA.
The purpose of this study was to narrow the 97 member gene list, to a smaller number of genes in order to focus studies on a limited number of genes/SNPs that might explain prostate cancer disparity in African Americans.
We performed genotype-phenotype, SNP and expression transcript levels correlations using HapMap Yoruba population with 85 of our 97 prostate candidate genes using SCAN database.
Findings revealed an association of SNPs surrounding ABCD3 gene with basal gene expression of RanGAP1 is important in prostate tumors in AA. Hence, to confirm our results in clinical biospecimen, we monitored expression of ABCD3 in a novel panel of African American and Caucasian prostate cancer paired cell lines. The LNCaP, C4-2B showed 2-fold increase; MDA-2PC-2B cell line, derived from AA, showed highest fold-change, 10-fold. The EGFR over expressing DU-145 WT cell line exhibited a 4-fold increase in expression relative to non transfected DU-145 prostate cell lines. Furthermore, Ingenuity Network analysis implicated our AA prostate candidate genes are involved in three network hubs, ERK, MapK and NFkB pathways.
Taken together, these findings are intriguing because other members of the ABC gene family, namely, ABCC3, ABCD1, and ABCD2 have been shown to confer chemoresistance in certain cancer types. Equally important, is the fact that activation of the MapK/ERK pathway via EGFR stimulation is vital for increased transcription of numerous cancer related genes. It is especially noteworthy that overexpression of EGFR has been widely observed in AA prostate tumors. Collectively our findings lead us to think that a novel signaling cascade, through which increased aggressiveness and chemoresistance is achieved, may explain prostate cancer health disparity in AA males and the nature of aggressive CaP tumors in general.
Prostate cancer (CaP) is the second leading cause of cancer-related death among all men in the United States. However, incidence and mortality rates for this disease vary substantially among geographic areas and ethnic groups. Most notably African American men (AA) in the United States have the highest risk (19%) of developing prostate cancer, and due to the development of more aggressive disease, they have more than twice the mortality rate observed for other racial and ethnic groups . The explanation for these differences is still unknown; however proposed explanations include genetic factors, dietary factors, behavioral factors, biological tumor aggressiveness, socio-economic factors and gene-environment interaction [2–35]. While AA race/ethnicity is one of the three primary non-modifiable risk factors confirmed for CaP, there are only a few published cDNA microarray studies [36–38] that have focused on gene expression differences in AA tumors compared to CA in an attempt to understand prostate cancer health disparity. Previously we identified 97 genes differentially expressed in AA prostate tumors. To narrow down this number of genes, we utilized advance bioinformatics methods. In the present study we performed genotype-phenotype or SNP and expression transcript level correlations of HapMap lymphoblastoid cell lines from Yoruba population to the 97 prostate candidate genes in AA, in an attempt to ferret out genetic variants associated with AA population. In addition, we used Ingenuity pathway analysis to calculate the probability of finding our set of candidate genes within a given pathway(s) to establish probable signal transduction mechanisms.
Microarray prostate candidate gene list for AA tumors
The gene list used in this study was obtained from our previously published cDNA microarray study .
SCAN database analysis to look for gene-gene interactions
SCAN is a large-scale database of genetics and genomics data associated to a web-interface and a set of methods and algorithms that can be used for mining the data in it (http://www.scandb.org/newinterface/about.html). Information on the relationship between SNPs and expression transcript levels (eQTLs) that is served by SCAN comes from a series of publications describing studies characterizing eQTLs in lymphoblastoid cell lines from HapMaP Caucasian (CEU) and Yoruba (YRI) samples for which transcript levels have been assayed using the Affymetrix Human Exon 1.0 ST Array [39–44].
The SCAN database contains two categories of SNP annotations: (1) Physical-based annotation or SNPs categorized according to their position relative to genes (intronic, antigenic, etc.) and according to linkage disequilibrium (LD) patterns (an intergenic SNP can be annotated to a gene if it is in LD with variation in the gene). (2) Functional annotation where SNPs are classified according to their effects on expression levels, i.e. whether they are eQTLs for that gene. Information on physical, functional and LD annotation served on the SCAN database comes directly from public resources, including HapMap (release 23a), NCBI (dbSNP 129), or is information created by using data downloaded from these public resources. In SCAN database, genotype data for the YRI samples was obtained from HapMap project (http://www.hapmap.org). Genotype and gene annotations were obtained from NCBI, dbSNP 129.
We uploaded appropriate gene identifiers for our prostate candidate genes and queried for SNPs that are significantly associated with expression of prostate candidate genes in Yoruba (YRI) population in lymphoblastoid cell lines. SCAN genetic and genomic data for the Yoruba Population in Ibaden, Nigeria, Africa was used because of close ancestral ties of Nigerians to African Americans. The SCAN analysis output reports a list of SNPs in gene(s) that predict expression quantitative trait loci found in mRNA profiles from YRI with p-values less than 0.0001.
Hugo gene symbols
To enter a list of genes into SCAN, it is first necessary to use the HUGO (Hu man G enome O rganization) gene symbol - the unique gene name and symbol given to each human gene by The HUGO Gene Nomenclature Committee (HGNC). From our 97 gene list, we were able to obtain HUGO gene symbols for 85 of the 97 genes (hereafter referred to as 85/97).
Ingenuity pathway analysis
Ingenuity software (http://www.ingenuity.com/) was used for pathway analysis. Ingenuity software calculates p-value for the probability of finding a set of genes within a given pathway. Fisher's exact test was used to calculate the p-values associated with finding 536 prostate genes obtained during this study (which includes 85/97 candidate genes, from previous differential expression study  and 451 candidate genes that are corresponding to Cis- regulatory SNPs, that are significantly associated with the 85 candidate genes) within a annotated network from Ingenuity Knowledge Base.
RT-PCR validation in novel panel of prostate cancer lines
RT-PCR assay was done using a 7500 FAST Real-Time ABI System.
Briefly, total RNA from each cultured prostate cell line was extracted, separately, with RNAzol B (Tel-Test Inc., Friedswood, Tx) according to the manufacturer’s protocol and quantified with Nucleic Acid Quantitation Kit (NBI, Plymouth, MN). Total RNA (1 ug) was reverse transcribed into cDNA with RT2 First strand Kit (SABiosciences/A Qiagen Company)) and 1.10 of the reverse-transcribed product from each sample was used for PCR to amplify ABCD3 gene, using a RT2 qPCR Primer Assay for Human ABCD3 (SABiosciences/A Qiagen Company) The expression of GAPDH was used as an internal control/housekeeping gene. Experimental conditions for the ABCD3 gene was optimized to analyze the amplified product in the linear range of amplification by adjusting amplification cycles for each set of primers. The expected band size (bp) size of the PCR product was 83, as described by vendor (SABiosciences).
Novel prostate cancer cell lines: description
Non-malignant (RC-77N/E) and malignant (RC-77T/E) prostate cells were derived from an African American prostate cancer patient and both are androgen sensitive . RC-77N/E cells were isolated from pathological normal cells, while RC-77T/E were derived from stage T3 tumor. Both cell lines are cultured in Keratinocyte Serum-Free Medium (KGM) Life Technologies, Gaithersburg, Md., USA), supplemented with bovine pituitary extract (BPE), recombinant epidermal growth factor (rEGF), 1% (v/v) penicillin-streptomycin-neomycin (PSN) antibiotic mixtures and 1% (v/v) amphotericin B (KGM) (Life Technologies, Gaithersburg, MD, USA). MDA-2PC-2B, also derived from an African American patient are androgen dependent, metastatic and are cultured in F12 K medium. DU-145, a cell line originally derived from a brain metastasis of a human prostate adenocarcinoma  retains the androgen independence of the original tumor and does not express a functional AR . This cell line has both LHRH-R and epidermal growth factor receptors (EGFR) and produces the EGFR ligands, transforming growth factor α (TGF-α) and EGF [48, 49]. Utilizing established protocols, DU-145 cells were transfected by retroviral-containing EGFR constructs . The wild-type (WT) EGFR construct is a full-length cDNA derived from a placental cDNA library. Cells expressing WT EGFR at levels that escape downregulation demonstrate enhanced invasiveness in vitro . LNCaP cells were derived from a lymph node metastasis . The Caucasian LNCaP, C42-B prostate cancer cell lines were maintained in T-medium as previously described.
Origin of the 97 prostate candidate genes
To detect for gene-gene interactions in AA prostate tumors in African American males, we used a cDNA microarray gene list obtained from a pilot project cDNA microarray comparison study of prostate tumor gene expression in AA and CA . To obtain differentially expressed gene or the gene list, we used four snap frozen tumors and four snap frozen non-tumor matched controls, each, from AA and CA . All tumors had a Gleason score of six. Gene expression profiles were measured for each of the micro dissected CaP tumor samples using Affymetrix U133A human arrays as described in . Each of the 8 prostate tumors and 8 matched controls underwent single hybridization and was arrayed individually (i.e. samples were not pooled). Data from the micro array CEL files were uploaded to R-Bioconductor for analysis . We paired normal AA tissue to tumor AA and paired normal CA to tumor CA to generate for case paired t-tests for each race group; gene lists of differentially expressed genes in AA Tumor vs. AA controls and of CA Tumor vs. CA controls were generated. We looked for differentially expressed genes that met the filtering criteria of a 4.0-fold change and a p< 0.0001. Neither the comparison of AA tumor to AA controls nor the comparison CA tumors to CA controls yielded genes that met both parts of our filtering criteria. However, when we looked at the ratio of CA tumor/CA normal to AA tumor/AA normal (case-matched ratios-race group tests for specific expression trends) we found 97 statistically significant, differentially expressed genes with 4-fold or greater fold change and p<0.0001. It was necessary to ratio the ratios to control for the high degree of genetic variation in AA tumor and AA non-tumor samples.
Scan database SNP and expression transcript level association results
After uploading our 85/97 prostate candidate genes with appropriate HUGO gene symbols and querying for SNPs in our 85/97 significantly associated with SNPs in the HapMap Yoruba (YRI) population; approximately, 26527 genotype-phenotype associations were obtained with a p-value < 10-3, of which 17542/26527 associations had a p-value <10-4 ( data not shown)
CaP candidate genes found in ERK, MapK, NFKB pathways
ABCD3 gene highly expressed in aa metastatic prostate cancer lines
To address the underlying genetic cause of prostate cancer burden in African Americans, we previously obtained a cohort of normal tumor paired samples from African American and Caucasian men, and looked for differential gene expression within each group. Utilizing a strict filtering criteria, we observed over 97 differentially expressed genes in our African American vs. Caucasian sample set . To further narrow the list to genes of utmost importance in prostate disease onset, we used a genome-wide association approach that allowed us to rapidly scan for SNPs in the genome of healthy Yorubai population (Yorubai from Ibaden, Nigeria) that might possibly be associated with our 85/97 prostate candidate genes. We utilized the HapMap database of YBI, Nigerian lymphoblastoid cell lines, since there are a limited number of SNP databases containing African American patients. Most importantly the Yorubai population rather than the Caucasian (CEU) population was utilized because the close ancestral ties  between West African Africans and African Americans would increase our chances of finding similar genetic variants associated with prostate disease in men of African descent (Nigerians and African Americans). Approximately 536 genes were identified in our association study as described in methods section (85 candidate genes + 451 cis-regulatory genes) that are associated with the 85/97 candidate genes. Herein we report that a significant number of direct gene-gene interactions were found, however the most significant interactions were observed on chromosome 1 and chromosome 12. Given the importance of these chromosomes in prostate disease, it was appropriate to investigate ABCD3 gene involvement in African American prostate cancer. Our analysis of gene-gene interactions on chromosome 1 and 12 revealed that ABCD3/RanGAP1 and STXBP and TMTC2 gene showed the strongest associations. Of these the ABCD3/RanGAP1 genes were predicted to have the most significant interactions. As such neither ABCD3 or RanGAP1 expression has been implicated in prostate cancer, therefore we chose to focus on ABCD3. The A TP-b inding c assette genes consist of various subfamilies, are typically expressed in both normal and cancer cells. Their functions have been implicated in acquired Multidrug Resistance, MDR, in cancer cell lines. For example, recent reports have shown that MCF-7/AdVp3000 cells that were derived by selection for growth in the presence of doxorubicin, exhibit a 459-fold overexpression of ABCC3 relative to the parental cell line . A similar situation in prostate cancer cell lines has been observed as MDR1/Pgp/ABCB1 and multidrug resistance-associated protein-1(MRP1/ABCC1), with the half ABC transporter, breast cancer resistance protein BCRP/ABCG2, is able to selectively isolate the putative prostate stem cells from the prostate tissue microenvironment through constitutive efflux of androgen and protects the putative tumor stem cells from androgen deprivation, hypoxia, or adjuvant chemotherapy . These findings are supported by unpublished data, from Yates laboratory, that suggest that fluorescence-activated cell sorting, FACS isolation of the (SP) cells, selective for functional ABC transporter pumps, have higher in vivo tumorigenicity compared to other cell surface markers (unpublished data). Thus, it is possible that ABCD3 could possibly contribute to aggressive prostate cancer.
Multiple ABC family genes have been implicated to play a role in chemoresistance and progression of prostate and breast cancer, however given the large number of family subtypes only a few have been associated with prostate cancer progression to aggressive disease. Since ABCD3 gene expression has not been identified previously in prostate cancer, we verified this in commonly utilized prostate cancer cell lines, as well as in a normal and primary tumor cell line pair derived from an African American prostate cancer patient [45, 57]. As in prostate patient samples, ABCD3 was consistently overexpressed in the RC-77N/E/RC-77T/E, LNCaP/C4-2B models, with MDA-PC-2B cells exhibiting the highest expression (10-fold). This data is consistent with the expression of other members of the ABC gene family that have been implicated in prostate cancer, and serves as proof-of-principle evidence that ABCD3 overexpression is indeed correlated with prostate cancer progression. That MDA-2PC-2B cells exhibited the highest expression levels, further implicates a role for ABCD3 in African American prostate cancers.
To further substantiate the link of ABCD3 with other cell signaling molecules that contribute to prostate cancer, we utilized an indirect in silico ingenuity pathway analysis. ABCD3, showed a high probability of being found within three growth factor initiated network hubs involving ERK, MAPK and NFkB proteins. The ERK MAPK has been implicated in a number of pathophysiological events including androgen receptor signaling  and the epithelial-to-mesenchymal (EMT)  that occurs as cancer cells acquire the property to metastasize. That we observed a 4 fold increase in ABCD3 expression in an EGFR overexpressing DU-145 WT cell line compared to non-transfected DU-145 cells, highlights a putative novel regulator of ABCD3. EGFR is overexpressed in African American Prostate patients  and a robust activator of MAPK ERK in normal and cancer cell . Furthermore overexpression is sufficient to increase proliferation, invasion related EMT, and metastasis [49, 62, 63]. Thus, it appears that ABDC3 is a novel prostate cancer associated gene, that could, in part, be regulated by EGFR signaling.
Although further studies to investigate the ABCD3/RanGAP1 relationship need to be conducted, our results clearly illustrate the utility of high density SNP analysis, in conjunction with appropriate cell lines that represent the clinical conditions, to identify regulatory genes in prostate cancer. Although a more in-depth analysis of the exact role of ABCD3 in such events as cell proliferation, and chemoresistance is warranted and are underway. The results of this study provide a rationale for use of DU-145/DU-145WT and MDA-PC-2B as culture models to study molecular mechanisms associated with the health disparity in African American prostate cancer patients.
Limitation of study
The 97 member candidate gene list was derived from a limited number of prostate tumor samples and matched control from AA and CA. Nonetheless, approximately, 26527 genotype-phenotype associations were obtained with a p-value < 10-3, of which 17542/26527 associations has a p-value <10-4. The associations with the highest P-values showed two distinct association; one of which has led us to think that the ABC gene family plays an important role in prostate cancer aggressiveness and chemoresistance.
We acknowledge DoD Grant # W81XWH-04-1-0326 and NIH/NCRR/RCMI Grant # 5G12RR003020-26 to R.R.R; Mayo Clinic Dept of Medical Informatics for support services to K.R.K; Grant# G12RR03059-21A1 to C.Y; RCMI Cancer Cluster for provided networking opportunities among its investigators ( R.R.R. and C. Y.). Special thanks to Karunya Kandimalla for introducing R.R.R. to K.R.K.
This article has been published as part of Infectious Agents and Cancer Volume 6 Supplement 2, 2011: Proceedings of the First Biennial Conference on the Science of Global Prostate Cancer Disparities in Black Men. The full contents of the supplement are available online at http://www.infectagentscancer.com/supplements/6/S2.
- American Cancer Society Facts and Figures (2008). Atlanta: American Cancer SocietyGoogle Scholar
- Powell IJ: Keynote address: prostate cancer among African-American men--from the bench to the community. Prostate cancer and African-American men. Oncology (Williston Park). 1997, 11 (5): 599-605. discussion 606-15 passim. Review.PMID: 9159788Google Scholar
- Powell IJ: Prostate cancer in the African American: is this a different disease?. Semin Urol Oncol. 1998, 16 (4): 221-6. Review.PMID: 9858329PubMedGoogle Scholar
- Giovannucci E, Platz EA, Stampfer MJ, Chan A, Krithivas K, Kawachi I: The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia. Urology. 1999, 53: 121-5. 10.1016/S0090-4295(98)00468-3. doi:10.1016/S0090-4295(98)00468-3View ArticlePubMedGoogle Scholar
- Caskey CT, Pizzuti A, Fu YH, Fenwick RG, Nelson DL: Triplet repeat mutations in human disease. Science. 1992, 256 (5058): 784-9. 10.1126/science.1589758. doi:10.1126/science.1589758View ArticlePubMedGoogle Scholar
- Platz EA, Rimm EB, Willett WC, Kantoff PW, Giovannucci E: Racial variations in prostate cancer incidence and in hormonal system markers among male health professionals. J Natl Cancer Inst. 2000, 92 (24): 2009-17. 10.1093/jnci/92.24.2009. doi:10.1093/jnci/92.24.2009View ArticlePubMedGoogle Scholar
- Smith GE, DeHaven MJ, Grundig JP, Wilson GR: African-American males and prostate cancer: assessing knowledge levels in the community. J Natl Med Assoc. 1997, 89 (6): 387-91.PubMed CentralPubMedGoogle Scholar
- Barber KR, Shaw R, Folts M, Taylor DK, Ryan A, Hughes M: Differences between African-American and Caucasian men participating in a community-based prostate cancer screening program. J Community Health. 1998, 23 (6): 441-51. 10.1023/A:1018758124614. doi:10.1023/A:1018758124614View ArticlePubMedGoogle Scholar
- Abbott RR, Taylor DK, Barber K: A comparison of prostate knowledge of African-American and Caucasian men: Changes from prescreening baseline to post-intervention. Cancer J Sci Am. 1998, 4 (3): 175-7.PubMedGoogle Scholar
- Steele CB, Miller DS, Maylahn C, Uhler RJ, Baker CT: Knowledge, attitudes, and screening practices among older men regarding prostate cancer. Am J Public Health. 2000, 90 (10): 1595-600. 10.2105/AJPH.90.10.1595.PubMed CentralView ArticlePubMedGoogle Scholar
- Agho AO, Lewis MA: Correlates of actual and perceived knowledge of prostate cancer among African Americans. Cancer Nurs. 2001, 24 (3): 165-71. 10.1097/00002820-200106000-00001. doi:10.1097/00002820-200106000-00001View ArticlePubMedGoogle Scholar
- Ashford AR, Albert SM, Hoke G, Cushman LF, Miller DS, Bassett M: Prostate carcinoma knowledge, attitudes, and screening behavior among African-American men in Central Harlem, New York City. Cancer. 2001, 91 (1): 164-72. 10.1002/1097-0142(20010101)91:1<164::AID-CNCR21>3.0.CO;2-A. doi:10.1002/1097-0142(20010101)91:1<164::AID-CNCR21>3.0.CO;2-AView ArticlePubMedGoogle Scholar
- Magnus M: Prostate cancer knowledge among multiethnic black men. J Natl Med Assoc. 2004, 96 (5): 650-6.PubMed CentralPubMedGoogle Scholar
- Richardson JT, Webster JD, Fields NJ: Uncovering myths and transforming realities among low-SES African-American men: Implications for reducing prostate cancer disparities. J Natl Med Assoc. 2004, 96 (10): 1295-302.PubMed CentralPubMedGoogle Scholar
- Woods VD, Montgomery SB, Belliard JC, Ramirez-Johnson J, Wilson CM: Culture, black men, and prostate cancer: What is reality?. Cancer Control. 2004, 11 (6): 388-96.PubMed CentralPubMedGoogle Scholar
- Forrester-Anderson IT: Prostate cancer screening perceptions, knowledge, and behaviors among African American men: Focus group findings. J Health Care Poor Underserved. 2005, 16 (4, Suppl A): 22-30. 10.1353/hpu.2005.0122. doi:10.1353/hpu.2005.0122View ArticlePubMedGoogle Scholar
- Jones AR, Shipp M, Thompson CJ, Davis MK: Prostate cancer knowledge and beliefs among black and white older men in rural and urban counties. J Cancer Educ. 2005, 20: 96-102. 10.1207/s15430154jce2002_10. doi:10.1207/s15430154jce2002_10View ArticlePubMedGoogle Scholar
- Ross LE, Uhler RJ, Williams KN: Awareness and use of prostate-specific antigen test among African-American men. J Natl Med Assoc. 2005, 97 (7): 963-71.PubMed CentralPubMedGoogle Scholar
- Pruthi RS, Tornehl C, Gaston K, Lee K, Moore D, Carson CC: Impact of race, age, income, and residence on prostate cancer knowledge, screening behavior, and health maintenance in siblings of patients with prostate cancer. Eur Urol. 2006, 50 (1): 64-9. 10.1016/j.eururo.2005.09.024. doi:10.1016/j.eururo.2005.09.024View ArticlePubMedGoogle Scholar
- McWhorter WB, Schatzkin AG, Horm JW, Brown CC: Contribution of socioeconomic status to Black/White differences in cancer incidence. Cancer. 1989, 63: 982-7. 10.1002/1097-0142(19890301)63:5<982::AID-CNCR2820630533>3.0.CO;2-I. doi:10.1002/1097-0142(19890301)63:5<982::AID-CNCR2820630533>3.0.CO;2-IView ArticlePubMedGoogle Scholar
- Baguet CR, Horm JW, Gibbs T, Greewald P: Socioeconomic factors and cancer incidence among Blacks and Whites. J Natl Cancer Inst. 1991, 83: 551-7. 10.1093/jnci/83.8.551. doi:10.1093/jnci/83.8.551View ArticleGoogle Scholar
- Robbins AS, Whittemore AS, Van Den Eeden SK: Race, prostate cancer survival, and membership in a large health maintenance organization. J Natl Cancer Inst. 1989, 90 (13): 986-90. doi:10.1093/jnci/90.13.986View ArticleGoogle Scholar
- Brawn PN, Johnson EH, Kuhl DL, Riggs MW, Speights VO, Johnson CFIII: Stage at presentation and survival of white and black patients with prostate carcinoma. Cancer. 1993, 71 (8): 2569-73. 10.1002/1097-0142(19930415)71:8<2569::AID-CNCR2820710822>3.0.CO;2-R. doi:10.1002/1097-0142(19930415)71:8<2569::AID-CNCR2820710822>3.0.CO;2-RView ArticlePubMedGoogle Scholar
- Ndubuisi SC, Kofie VY, Andoh JY, Schwartz EM: Black-white differences in the stage at presentation of prostate cancer in the District of Columbia. Urology. 1995, 46 (1): 71-7. 10.1016/S0090-4295(99)80162-9. doi:10.1016/S0090-4295(99)80162-9View ArticlePubMedGoogle Scholar
- Freedland SJ, Amling CL, Dorey F, Kane CJ, Presti JC, Terris MK: Race as an outcome predictor following radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Urology. 2002, 60: 670-4. 10.1016/S0090-4295(02)01847-2. doi:10.1016/S0090-4295(02)01847-2View ArticlePubMedGoogle Scholar
- Polednak AP, Flannery JT: Black versus white racial differences in clinical stage at diagnosis and treatment of prostatic cancer in Connecticut. Cancer. 1992, 70: 2152-8. 10.1002/1097-0142(19921015)70:8<2152::AID-CNCR2820700824>3.0.CO;2-#. doi:10.1002/1097-0142(19921015)70:8<2152::AID-CNCR2820700824>3.0.CO;2-#View ArticlePubMedGoogle Scholar
- Moul JW, Sesterhenn IA, Connelly RR, Douglas T, Srivastava S, Mostofi FK: Prostate-specific antigen values at the time of prostate cancer diagnosis in African American men. J Am Med Assoc. 1995, 274: 1277-81. 10.1001/jama.274.16.1277.View ArticleGoogle Scholar
- Horner RD: Racial variation in cancer care: A case study of prostate cancer. Cancer Treat Res. 1998, 97: 99-114. 10.1007/978-0-585-30498-4_8. doi:10.1007/978-0-585-30498-4_8View ArticlePubMedGoogle Scholar
- Brawley OW, Knopf K, Thompson I: The epidemiology of prostate cancer part II: The risk factors. Semin Urol Oncol. 1998, 16: 193-201.PubMedGoogle Scholar
- Fowler JE, Bigler S, Bowman G, Kilambi N: Race and cause specific survival with prostate cancer: Influence of clinical stage, Gleason score, age and treatment. J Urol. 2000, 163 (1): 137-42. 10.1016/S0022-5347(05)67989-X. doi:10.1016/S0022-5347(05)67989-XView ArticlePubMedGoogle Scholar
- Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR: Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst. 1995, 87 (9): 652-61. 10.1093/jnci/87.9.652. doi:10.1093/jnci/87.9.652View ArticlePubMedGoogle Scholar
- Freedland SJ, Isaacs WB: Explaining racial differences in prostate cancer in the United States: Sociology or biology?. Prostate. 2005, 62: 243-52. 10.1002/pros.20052. doi:10.1002/pros.20052View ArticlePubMedGoogle Scholar
- Guo Y, Sigman DB, Borkowski A, Kyprianou N: Racial differences in prostate cancer growth: Apoptosis and cell proliferation in Caucasian and African-American patients. Prostate. 2000, 42: 130-6. 10.1002/(SICI)1097-0045(20000201)42:2<130::AID-PROS7>3.0.CO;2-3. doi:10.1002/(SICI)1097-0045(20000201)42:2<130::AID-PROS7>3.0.CO;2-3View ArticlePubMedGoogle Scholar
- Ross R, Bernstein L, Judd H, Hanisch R, Pike M, Henderson B: Serum testosterone levels in healthy young black and white men. J Natl Cancer Inst. 1986, 76: 45-8.PubMedGoogle Scholar
- Ross R, Bernstein L, Lobo RA, Shimizu H, Stanczyk FZ, Pike MC: 5-alpha-reductase activity and risk of prostate cancer among Japanese and US White and Black males. Lancet. 1999, 339: 887-9. doi:10.1016/0140-6736(92)90927-UView ArticleGoogle Scholar
- Reams RR, Agrawal D, Davis M, Yoder S, Odedina F, Kumar N, Higginbotham J, Akinremi T, Suther S, Soliman K: Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study. Infectious Agents and Cancer. 2009, 4 (Suppl 1): S3-PubMed CentralView ArticlePubMedGoogle Scholar
- Wallace TA, Prueitt RL, Yi M, Howe TM, Gillespie JW, Yfantis HG, Stephens RM, Caporaso NE, Loffredo CA, Ambs S: Tumor Immunobiological Differences in Prostate Cancer between African-American and European-American Men. Cancer Res. 2008, 68 (3): 927-936. 10.1158/0008-5472.CAN-07-2608.View ArticlePubMedGoogle Scholar
- Timofeeva OA, Zhang X, Ressom HW, Varghese RS, Kallakury BV, Wang K, Ji Y, Cheema A, Jung M, Brown ML, Rhim JS, Dritschilo A: Enhanced expression of SOS1 is detectable in prostate cancer epithelial cells from African-American men. Int J Oncol. 2009, 35 (4): 751-60.PubMed CentralPubMedGoogle Scholar
- Gamazon ER, Zhang W, Konkashbaev A, Duan S, Kistner EO, Nicolae DL, Dolan ME, Cox NJ: SCAN: SNP and copy number annotation. Bioinformatics. 2010, 26 (2): 259-62. 10.1093/bioinformatics/btp644. Epub 2009 Nov 17.PMID: 19933162 [PubMed - indexed for MEDLINE]PubMed CentralView ArticlePubMedGoogle Scholar
- Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ: Trait-Associated SNPs Are More Likely to Be eQTLs: Annotation to Enhance Discovery from GWAS. PLoS Genet. 2010, 6 (4): e1000888-10.1371/journal.pgen.1000888. doi:10.1371/journal.pgen.1000888 PMID 20369019PubMed CentralView ArticlePubMedGoogle Scholar
- Gamazon ER, Zhang W, Konkashbaev A, Duan S, Kistner E, Nicolae DL, Dolan ME, Cox NJ: SCAN: SNP and copy number annotation. Bioinformatics. Advance Access published on November 17, 2009, doi:10.1093/bioinformatics/btp644 PMID 19933162Google Scholar
- Duan S, Huang RS, Zhang W, Bleibel WK, Roe CA, Clark TA, Chen TX, Schweitzer AC, Blume JE, Cox NJ, Dolan ME: Genetic Architecture of Transcript-Level Variation in Humans. Amer. J. Human Genetics. 2008, 82: 1101-1113. 10.1016/j.ajhg.2008.03.006. PMID 18439551View ArticleGoogle Scholar
- Zhang W, Duan S, Kistner EO, Bleibel WK, Huang RS, Clark TA, Chen TX, Schweitzer AC, Blume JE, Cox NJ, Dolan ME: Evaluation of Genetic Variation Contributing to Differences in Gene Expression Between Populations. Amer. J. Human Genetics. 2008, 82: 631-640. 10.1016/j.ajhg.2007.12.015. PMID 18313023View ArticleGoogle Scholar
- Duan S, Zhang W, Bleibel WK, Cox NJ, Dolan ME: SNPinProbe_1.0: A database for filtering out probes in the Affymetrix GeneChip(R) Human Exon 1.0 ST array potentially affected by SNPs. Bioinformation. 2008, 2 (10): 469-70. PMID 18841244PubMed CentralView ArticlePubMedGoogle Scholar
- Theodore S, Sharp S, Zhou J: Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient. International journal of oncology. 37: 1477-82.Google Scholar
- Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF: Isolation of a human prostate carcinoma cell line (DU 145). International journal of cancer. 1978, 21: 274-81. 10.1002/ijc.2910210305.View ArticleGoogle Scholar
- Dondi D: Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH) agonists on xenografts of the DU 145 human androgen-independent prostate cancer cell line in nude mice. Int J Cancer. 1998, 76 (4): 506-11. 10.1002/(SICI)1097-0215(19980518)76:4<506::AID-IJC11>3.0.CO;2-5.View ArticlePubMedGoogle Scholar
- Jungwirth A, Pinski J, Galvan G: Inhibition of growth of androgen-independent DU-145 prostate cancer in vivo by luteinising hormone-releasing hormone antagonist Cetrorelix and bombesin antagonists RC-3940-II and RC-3950-II. Eur J Cancer. 1997, 33: 1141-8. 10.1016/S0959-8049(97)00072-5.View ArticlePubMedGoogle Scholar
- Turner T, Chen P, Goodly LJ, Wells A: EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. Clinical & experimental metastasis. 1996, 14: 409-18. 10.1007/BF00123400.View ArticleGoogle Scholar
- Wells A, Welsh JB, Lazar CS, Wiley HS, Gill GN, Rosenfeld MG: Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. Science. 1990, 247: 962-964. 10.1126/science.2305263.View ArticlePubMedGoogle Scholar
- Xie H, Turner T, Wang MH, Singh RK, Siegal GP, Wells A: In Vitro invasiveness of DU-145 human prostate carcinoma cells is modulated by EGF receptor-mediated signals. Clin Exp Metastasis. 1995, 13 (6): 407-19. 10.1007/BF00118180.View ArticlePubMedGoogle Scholar
- Horoszewicz JS: The LNCaP cell line--a new model for studies on human prostatic carcinoma. Prog Clin Biol Res. 1980, 37: 115-32.PubMedGoogle Scholar
- Tusher VG, Tibshirani R, Chu G: Significance analysis of micro arrays applied to the Ionizing radiation response. Proc Nation Acad Sci USA. 2001, 98 (9): 5116-21. 10.1073/pnas.091062498.View ArticleGoogle Scholar
- Odedina FT, Akinremi TO, Chinegwundoh F, Roberts R, Yu D, Reams RR, Freedman ML, Rivers B, Green BL, Kumar N: Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa. Infect Agent Cancer. 2009, 10 (4 Suppl 1): S2-View ArticleGoogle Scholar
- Liu Y, Peng H, Zhang JT: Expression profiling of ABC transporters in a drug-resistant breast cancer cell line using AmpArray. Mol Pharmacol. 2005, 68: 430-8.PubMedGoogle Scholar
- Huss WJ, Gray DR, Greenberg NM, Mohler JL, Smith GJ: Breast cancer resistance protein-mediated efflux of androgen in putative benign and malignant prostate stem cells. Cancer research. 2005, 65: 6640-50. 10.1158/0008-5472.CAN-04-2548.View ArticlePubMedGoogle Scholar
- Theodore SC, Rhim JS, Turner T, Yates C: MiRNA 26a expression in a novel panel of African American prostate cancer cell lines. Ethn Dis. 20: S1-96-100.Google Scholar
- Peterziel H, Mink S, Schonert A, Becker M, Klocker H, Cato AC: Rapid signalling by androgen receptor in prostate cancer cells. Oncogene. 1999, 18: 6322-9. 10.1038/sj.onc.1203032.View ArticlePubMedGoogle Scholar
- Odero-Marah VA, Wang R, Chu G: Receptor activator of NF-kappaB Ligand (RANKL) expression is associated with epithelial to mesenchymal transition in human prostate cancer cells. Cell Res. 2008, 18: 858-70. 10.1038/cr.2008.84.View ArticlePubMedGoogle Scholar
- Shuch B, Mikhail M, Satagopan J: Racial disparity of epidermal growth factor receptor expression in prostate cancer. J Clin Oncol. 2004, 22: 4725-9. 10.1200/JCO.2004.06.134.View ArticlePubMedGoogle Scholar
- Gan Y, Shi C, Inge L, Hibner M, Balducci J, Huang Y: Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells. Oncogene. 29: 4947-58.Google Scholar
- Yates C, Wells A, Turner T: Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline. British journal of cancer. 2005, 92: 366-PubMed CentralPubMedGoogle Scholar
- Yates CC, Shepard CR, Stolz DB, Wells A: Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. British journal of cancer. 2007, 96: 1246-52. 10.1038/sj.bjc.6603700.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.