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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., The original document contains color images.

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.