Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin
Final rept. 1 Apr 2002-31 Mar 2006
SAINT LUKE'S-ROOSEVELT INST FOR HEALTH SCIENCES NEW YORK NY OFFICE OF GRANTS AND RESEARCH ADMINISTRATION
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The plasma protein sex hormone-binding globulin SHBG not only binds estrogens in plasma but also is part of an estrogen signal transduction system that starts with a receptor RSHBG for SHBG on breast cell membranes. The SHBG-RSHBG complex is activated by an appropriate steroid hormone eg. estradiol E2 forming the new complex E2-SHBG-RSHBG to trigger a second messenger system to produce cAMP minutes after steroid binding. Frozen sections of normal and cancerous breast cells stain with anti-SHBG antibodies and these same cells contain SHBG mRNA. MCF-7 cells also make their own SHBG mRNA and protein. We present a complex picture of extra hepatic human SHBG gene expression including at least 12 different transcripts generated through alternative splicing and alternative promoter utilization. We have devised an inducible system to study SHBG protein expression in MCF-7 cells and have expressed tagged versions of SHBG in MCF-7 cells that will be useful for future studies on biologic function in breast cells and in breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research