Unique Approaches to Androgen Effects on Prostate Cancer
Final rept. 19 Jan 2004-18 Jan 2007
SAINT LUKE'S HOSPITAL CENTER NEW YORK
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Sex hormone-binding globulin SHBG is a plasma protein that binds andrngens and it acts as a transducer of androgen signaling at the plasma membrane of prostate cancer cells The human prostate cancer cell line LNCaP in addition to having a receptor for SHBG RSHBG produces its own SHBG We devised an inducible system to study SHBG protein expression in LNCaP cells and expressed tagged versions of SHBG in LNCaP cells that will also be useful for future studies on its biologic function We present a complex and novel picture of extrahepatic human SHBG gene expression including 21 different SHBG gene transcripts generated by alternative splicing 17 of which are newly descnbed and the use of three independent SHBG gene promoters including a novel prnmoter PN We used microarray technology to investigate the effect of SHBG on the DHT response of LNCaP cells and found evidence for RSHBG signaling and SHBG modulation of AR activity Further extended studies of the role of SHBG in prostate signaling and the modulation of SHBG expression in prostate cancer are warranted.
- Medicine and Medical Research