Abstract 1297: Engrailed-2 (EN2) represses the transcription of the CST6 tumour suppressor gene in prostate cancer

Abstract

Abstract Engrailed-2 (EN2) is a homeodomain-containing transcription factor that is expressed in prostate and breast tumours but not in normal adult tissue. Although EN2 protein is known to be secreted by prostate tumours and is a potential urine based biomarker of this disease, its function in prostate tumours is unknown. In this study we have used siRNA-mediated knock down of EN2 as well as forced over expression in prostate cancer cells. Although neither treatment has a significant effect on cell survival, we identify two key transcriptional targets of EN2, the tumour suppressor gene CST6 and the Death Receptor ligand TRAIL, the transcription of which are repressed and activated by EN2, respectively. EN2 synergises with epigenetic changes to silence CST6, and may function to block CST6 expression very early in the development of malignancy. Further, we show that EN2 protein can regulate gene transcription in non-malignant prostate cells when supplied externally, indicating that EN2 secretion by prostate tumour cells may be able to modify its microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1297. doi:1538-7445.AM2012-1297