Abstract C7: Analysis of high-risk prostate cancer markers at RNA and protein level.

Abstract

Abstract Background: In many developed countries, prostate cancer is the second leading cause of cancer-related deaths among men. Current diagnostic possibilities do not differentiate aggressive forms of prostate cancer from latent tumors. Therefore, having reliable and easy-to-detect marker is needed to treat this disease successfully. We determined potential novel tumor markers of high-risk prostate cancer (A) at the cell level, represented by cell lines 22Rv1 and PNT1A and (B) in the serum of 82 histologicaly -verified cases and 51 controls. Material and Methods: 22Rv1 cell line derived from primary prostate tumor and PNT1A cell line derived from normal prostate epithelium were used in our study. The real time PCR, electrophoretical separation technique, immunochemical detection and novel electrochemical analysis were used in tumor markers determination. Findings and Interpretation: Cell line 22Rv1 represents Gleason sum 9 primary tumor, compared to widely used cell lines PC-3, LNCaP and PD-145, representing metastasis, therefore, is more related to real tumor tissue. We determined RNA and protein level of genes alpha-methyl acyl-CoA racemase (AMACR), caveolin-1, metalothionein, p53, NF-kB, FOS, JUN, Ki-67, ZIP1 and ZnT-1. At the RNA level in cell lines we found significant (p < 0.01) down-regulation of Cav-1 (50-fold), NF-kB (11-fold) and others and significant (p < 0.01) up-regulation of metalothionein (2.4-fold), AMACR (8.4-fold), Ki-67 (2-fold) and zinc transporters ZnT-1 (25-fold) and ZIP1 (45-fold). Conversely, we observed down-regulation of metallothionein at protein level. In the serum of prostate cancer patients we found no significant differences in AMACR and caveolin-1 level and significantly (p < 0.001) higher metallothionein level suggesting metalothionein as a complementary marker to PSA. We found weak correlation of PSA on caveolin-1 (r = 0.41 at p = 0.002) and, interestingly, significant elevation of caveolin-1 in high-grade tumors (tumor stage 4 (2.3-fold elevation), Gleason sum 9, correlation at r = 0,29 at p = 0,028) suggesting caveolin-1 as potential high-risk prostate cancer marker. This study provides important new information about selected genes connected with prostate cancer and describes new electrochemical approaches for their determination in lower concentrations. Financial support from IGA MH of Czech republic no. NS10200–3 is greatly acknowledged. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C7.