Role of Orphan Nuclear Receptor CUP-TFII in Prostate Development and Tumorigenesis.

摘要

Orphan nuclear receptor COUP-TFII plays important roles in controlling diverse aspects of cell growth, development, differentiation and homeostasis. During the development, its expression is spatially and temporally restricted within mesenchymal cells of many organs that require interactions between the mesenchymal and epithelial compartments for proper development. To study the possible role of COUP-TFII during the development of prostate, we have investigated the expression pattern of COUP-TFII in mouse male reproductive organ at different stages by using in situ hybridization. Our results showed that COUP-TFII is highly expressed in mesenchymal cells surrounding ventral prostate, dorsal lateral prostate, vas deferens and other male reproductive organs, suggesting that COUP-TFII may be an important modulator for mesenchymal- epithelial interactions required for the normal prostate development and tumorgenesis of prostate cancer. To further study COUP-TFII's function during the carcinogenesis of prostate cancer, we have successfully generated adenoviral vectors that effectively express sense and antisense COUP-TFII mENA. Adenovirus- infected prostate cells or control cells were then introduced into asthymic nude mice to analyze the effect of COUP-TFII over- or under-expression on the ability of tumorigenesis of prostate cancer cell lines. For unknown reason, however, primary results were inconsistent and inconclusive. We are now investigating possible reasons and evaluating feasible solutions.