Autocine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin
Abstract
We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and this SHBG functions to alter the effects of estrogens within the breast cancer cell. We have shown that 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 rather than the intracellular estrogen receptor (ER). 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 within minutes after steroid binding. We have shown that frozen sections of normal and cancerous breast cells stain with anti-SHBG antibodies and these same cells contain SHBG mRNA. Further, the well-known breast cancer cell line, MCF-7, contains both SHBG mRNA and SHBG protein. The expression of SHBG by breast cancer cells raises the important question of how local regulation of SHBG synthesis and secretion affects both sequestration of steroid hormones within the breast, and estrogen induced signal transduction at the cell membrane. The local synthesis of SHBG is consistent with an autocrine/paracrine role in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425713
Entities
People
- William Rosner