Abstract A16: Different epigenetic mechanisms involved in the regulation of SFRP1 gene in prostate cancer

Among men, prostate cancer (PCa)[1] is the second most common cancer and the fifth cause of death worldwide [2]. Androgens play an important role in the development of the disease. For advanced PCa the standard therapy is androgen depletion. However, after 2 or 3 years a high percentage of patients become resistant to this therapy and castration resistant prostate cancer (CRPC) is developed. There is no successful treatment for CRPC, leading into death [3, 4]. Wingless pathway (WNT) is aberrantly activated in several cancer types and in PCa it is involved in AR activity modulation, promoting cancer development [5]. Secreted Frizzled Related Protein 1 (SFRP1) is commonly known as a WNT inhibitor and generally proposed as a tumor suppressor gene. SFRP1 can exert its tumor suppressor activity by inhibiting the AR transcriptional activity [6]. Usually in cancer, SFRP1 mRNA is down regulated and this is associated to increased DNA methylation at its promoter region [7]. In contrast, in PCa there are different reports suggesting SFRP1 repression in absence of DNA methylation [8]. In this work we aimed to investigate two different epigenetic mechanisms for SFRP1 silencing in PCa. For the in vitro model, we used normal prostate cells RWPE-1 and PCa cell lines: LNCaP, 22RV1 and PC3. We confirmed the correlation between mRNA expression loss and the increased DNA methylation of SFRP1 only in PC3 cells, but not in LNCaP and 22RV1, were instead of DNA methylation we found enrichment of H3...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Epigenetic Control of Transcription/ Elongation Source Type: research