A Cholesterol-Sensitive Regulator of the Androgen Receptor

Abstract : Published studies from our laboratory have shown that critical mediators of tumor cell physiology and behavior reside in cholesterol-rich, lipid raft membranes of prostate cancer cells. This project focuses on the RNA binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP-K) as a novel regulator of the androgen receptor (AR). We have found that hnRNP-K lies within the cholesterol-sensitive PI3K/Akt/PTEN/mTOR pathway and that hnRNP-K connects ErbB receptor/Akt-derived signals with androgenic signals, thereby directly linking peptide hormone and steroid hormone signal transduction mechanisms. Our hypothesis is that hnRNP-K mediates androgen sensitivity and growth and survival in prostate cancer cells by a mechanism involving the regulation of AR mRNA translation. The specific aims are: Aim 1. Determine the mechanism(s) underlying the effects of hnRNP-K on androgen sensitivity in prostate cancer cells. Aim 2. Determine whether changes in expression and/or subcellular localization alter the function of hnRNP-K and assess the physiologic consequences of these changes in prostate cancer cells.