Abstract 5206: Role of CtBP1 as a transcriptional corepressor in prostate cancer.

Abstract

Abstract Background: C-terminal Binding Protein 1 (CtBP1), a transcriptional co-repressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a critical role in multiple cancers. Earlier, we showed that CtBP1 is overexpressed in metastatic prostate cancer. Furthermore, our studies indicated a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. We also demonstrated the functional role of CtBP1 in regulating prostate cancer cell growth in vitro and tumor growth and metastasis in vivo. Methods and Results: Our gene expression profiling and bioinformatics analysis found that multiple potential tumor suppressors are reactivated upon CtBP1 knockdown in multiple prostate cancer cell lines. We next validated these targets of CtBP1-mediated repression by qRTPCR and western blotting using CtBP1 stable knockdown prostate cancer cell lines, and in normal prostate epithelial PrEC cells overexpressing CtBP1. Our studies confirmed that CtBP1 targets multiple genes including SP8 transcription factor and kallikrein-related peptidase 10 (KLK10) among others. Knockdown of the reactivated gene led to a reversion of these cells to a more aggressive phenotype. Furthermore, our studies confirmed that the CtBP1 target genes are down-regulated in metastatic prostate cancer. Conclusion: Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression by down-regulating the expression of multiple potential tumor suppressor genes. Thus, targeting CtBP1 in aggressive prostate cancer may have clinical significance. Citation Format: Balabhadrapatruni V. S. K. Chakravarthi, Satya Pathi, Heng Zheng, Javed Siddiqui, Lakshmi P. Kunju, Nallasivam Palanisamy, Sooryanarayana Varambally. Role of CtBP1 as a transcriptional corepressor in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5206. doi:10.1158/1538-7445.AM2013-5206