Accession Number:

ADA276024

Title:

Is Sex Hormone Binding Globulin Locally Produced in Breast Cancer

Descriptive Note:

Midterm rept. 2 Oct 1992-30 Sep 1993

Corporate Author:

MADIGAN ARMY MEDICAL CENTER TACOMA WA DEPT OF CLINICAL INVESTIGATION

Personal Author(s):

Report Date:

1993-10-15

Pagination or Media Count:

24.0

Abstract:

Sex hormone binding globulin SHBG is a high affinity binding protein for androgens and estrogens. This protein is normally produced in the liver, released into the blood and functions to replate the amount of free androgen or estrogen available for action at target organs. Recently, receptors for SHBG have been identified on steroid responsive tissues, including prostate carcinoma and endometrium. The goal of this series of experiments was to determine if mRNA for SHBG is expressed in breast cancer cell lines and tumor tissue. Two estrogen receptor positive cell lines were used, the ZR-75-1 and MCF-7. Initial experiments in which total RNA was extracted from the cells, followed by Northern blot analysis using a 500 bp 3 SHBG cDNA probe revealed SHBG mRNA in the ZR-75-1 cells, but no detectable message from the MCF-7 cells. The ZR-75-1 cells were used for studies investigating the transcriptional regulation of SHBG mRNA, which indicated that thyroxine may increase levels of SHBG mRNA, and estrogen and insulin may reduce levels. When MCF-7 cells were re- examined for SHBG RNA using PCR, specific message could be detected. Also, evidence of alternative splicing of the SHBG mRNA in breast cancer cells was found. Finally, amplification of RNA extracted from breast tumor tissue by PCR revealed the presence of SHBG mRNA in estrogen receptor positive tumors.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE