A Cholesterol-Sensitive Regulator of the Androgen Receptor
CHILDREN'S HOSPITAL CORP BOSTON MA
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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 PI3KAktPTENmTOR pathway and that hnRNP-K connects ErbB receptorAkt-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 mechanisms underlying the effects of hnRNP-K on androgen sensitivity in prostate cancer cells. Aim 2. Determine whether changes in expression andor subcellular localization alter the function of hnRNP-K and assess the physiologic consequences of these changes in prostate cancer cells.
- Anatomy and Physiology
- Medicine and Medical Research