Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone- Binding Globulin

摘要

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 (R-shbg) for SHBG on breast cell membranes. The SHBG-R-shbg complex is activated by an appropriate steroid hormone, e.g., estradiol (E2), (forming the new complex, E2-SHBG-R-shbg), 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 extrahepatic 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.