Pax 2 as a Therapeutic Target for Prostate Cancer

Medical University Of South Carolina, Charleston SC

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The PAX2 gene, a member of the PAX family of developmental control genes, is a transcriptional regulator that is essential for the differentiation of all intermediate mesoderm derived components of the urogenital system during early development. It has also been shown to be aberrantly overexpressed in a number of primary tumor tissues including prostate carcinoma, and confers a strong advantage for cancer cell growth. Silencing of PAX2 expression by RNA interference (siRNA) can cause rapid induction of apoptosis, and is thought to be required for the growth and survival of cancer cells. Recently, we have demonstrated that there is cancer-specific loss of human beta defensin 1 (DEFB1). Our studies have also found that DEFB1 causes apoptosis to prostate cancer cell lines which suggests that it may be a candidate tumor suppressor gene. In order to better understand the transcriptional machinery involved in DEFB1 expression, computational analysis of the DEFB1 promoter revealed a potential PAX2 binding site. As a result of these findings, we hypothesize that the loss of DEFB1 expression is due to the transcriptional repression by PAX2 and as a result, the loss of DEFB1 expression promotes tumor formation. [unreadable] [unreadable] [unreadable]