Androgen Regulation of p27 in the Normal and Neoplastic Prostate
Abstract
The cyclin dependent kinase inhibitor (CKI) p27 is a negative regulator of the cell cycle and a potential tumor suppressor gene. p27 deficient mice develop pituitary tumors and display increased body size suggesting a growth-inhibitory function in vivo. In addition, our preliminary data at the time the grant was submitted suggested that its expression in the prostate was regulated by androgens. The original aims of this proposal included 1) to determine whether p27 is regulated by androgens in the prostate utilizing a well established animal model; 2) to study the expression of p27 in both androgen dependent and independent human prostate cancer; 3) to assess the expression of novel isopeptidases involved in the regulation of the ubiquitin-proteasome pathway and identify those enzymes with a strong association with p27 and its degradation. Using the rat castration-regeneration model we found that expression of p27 is regulated primarily by ubiquitin-mediated degradation. Castration blocks the elevated p27 degradation characteristic of intact rat prostates, leading to increased expression of p27. During testosterone-induced regeneration, p27 degradation inversely correlates with p27 expression. These findings have been published (Waltregny et al, Mol Endocrinol 2001, 15:765-782). We also found a significant difference in the expression of p27 in Ad and Al tumors (Cai, Y.C. et al Lab Invest, 80, 545A, 2000 and manuscript in preparation). Finally, the isopeptidase KIA-190 (UBPO) was found to be overexpressed in 54% of prostate cancers but no correlation with p27 expression was found.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2001
- Accession Number
- ADA404718
Entities
People
- Massimo Loda
Organizations
- Dana–Farber Cancer Institute