Abstract B33: Determination of protein expression of candidate prostate cancer genes from a novel region on chromosome 7 identified in African American men

Abstract

Abstract In the United States, African American (AA) men are at 60% higher risk of developing prostate cancer than European American (EA) men, and AA men are 2.4 times more likely to die from prostate cancer than EA men. Although these disparities are frequently attributed to the greater aggressiveness of prostate cancer among AA men, it is not known what causes that prostate cancer aggressiveness in AA men. To identify germline genetic variation that could explain some of this disparity, our previous admixture mapping study identified a novel region on chromosome 7q31-34 where local ancestry was associated with risk of disease. The main objective of this study is to investigate whether candidate genes in this gene region show differences in protein product expression by cell line origin (AA vs. EA) and by cell line metastatic potential. We specifically examined the expression of three proteins sourced from this gene region through immunoblot analysis, filamin C (FLNC), glutamate receptor metabotropic B (GRM8), and cadherin-like and PC-esterase domain containing 1 (CPED1). The cell lines DU-145, PC3, LNCaP, RWPE1, and WPE1 were derived from biological specimens from EA men, whereas the PCa2b and the RC77T cell lines were sourced from AA men. The RWPE1 and WPE1 cell lines were derived from normal prostate cells, while the remaining cell lines were derived from metastatic prostate cancers. Using immunoblot analysis, we found that GRM8 is expressed at higher levels in the cell lines derived from AA men with prostate cancer compared to those from EA men with prostate cancer. In contrast, FLNC and CPED1 are expressed at higher levels in the cell lines from EA men with prostate cancer compared to those from AA men with prostate cancer. Interestingly, both FLNC and CPED1 expression is also low in the androgen sensitive LNCaP cell line. Importantly, these results are consistent with our fine mapping results in AA men, where the SNP with greatest evidence for association is located. Further, previous studies have demonstrated that the methylation status and mRNA expression of CPED1 and FLNC differed between prostate cancers from AA and EA men. Taken together, these results provide us with a foundation to test the relevance of these genes in prostate cancer growth and metastasis and contribute to our understanding of the molecular differences in prostate cancer between EA and AA men. Citation Format: Casey Wizner, Julie Ruterbusch, Nicole Kubinec, Gregory Dyson, Albert Levin, Julie Boerner, Cathryn Bock. Determination of protein expression of candidate prostate cancer genes from a novel region on chromosome 7 identified in African American men. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B33.