Small Molecules That Suppress IGF-Activated Prostate Cancers
Annual rept. 1 Apr 2004-31 Mar 2005
BAYLOR COLL OF MEDICINE HOUSTON TX
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Elevated serum levels of insulin-like growth factor 1 IGF1 have been found in prostate cancer patients, and IGF1-related signal transduction is thought to be an important factor in the development of prostate cancers. The goals of this project are to discover small organic molecules that suppress ICE-activated prostate cancers by cell-based screening and to analyze their action mechanisms. In the first year of funding, we discovered, from our collection of synthetic compounds, the drug-like compound we call 125B11 that suppress IGE1-dependent growth of prostate cancer cells but not serum-dependent growth. During this period of funding, we analyzed the mechanism of action of 125B11 to gain molecular insights into how IGE1 stimulates the growth of prostate cancer cells. DNA microarray and cell biological experiments indicated that 125B11 modulates the function of sterol regulatory element binding protein SREBP, a transcription factor that activates specific genes involved in cholesterol synthesis, endocytosis of low density lipoproteins, and the synthesis of both saturated and unsaturated fatty acids. Chemical genetics of 125B11 may reveal a novel crosstalk between fatty acid metabolism and prostate cancer progression.
- Anatomy and Physiology
- Medicine and Medical Research