Role of the Y-Located TSPY Gene in Prostatic Oncogenesis.

摘要

TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). It is aberrantly expressed in and could contribute to prostate cancer. The objectives of the project are: 1) to identify the oncogenic and/or tumor promoting properties of TSPY and 2) to correlate TSPY over-expression with prostatic oncogenesis in transgenic mice. During the funded penod we confirmed the involvement of TSPY in the initiation and/or early stages of prostate cancer and germ cell tumors. Ectopic TSPY expression potentiates cell proliferation (by shortening the G2/M phase) and tumor growth in nude mice leading to genome instability and gene dysregulation. Numerous oncogenes were up regulated and growth inhibitors were repressed in these TSPY- expressing cells. TSPY binds to cyclin B and exerts activating effects on cyclin B-CDK1 kinase activities. TSPY interacts with the elongation factor IA thereby enhancing the protein synthetic machinery and exacerbating tumor cell growth. TSPY transgene was expressed in the hyperplasic region in the prostates of transgenic mice thereby supporting its role(s) in either the initiation and/or early stages of prostatic carcinogenesis. Our results have provided significant insights on the role of TSPY in prostatic oncogenesis and development of diagnostic therapeutic and preventive strategies for prostate cancer.