Cited by 109Estrogen and related hormone effectsBreast Cancer Treatment StudiesProstate Cancer Treatment and Research

Progestin Inhibition of Progesterone Receptor Gene Expression in Human these steroids is determined in part by the cellular Breast Cancer Cells

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Alexander, Ian E., Clarke, Christine L., Shine, John, Sutherland, Robert L.·1989·Molecular Endocrinology

Abstract

The present study was designed to investigate whether inhibition of progesterone receptor (PR) gene transcription and/or regulation of PR mRNA half-life were involved in the progestin-mediated decrease of PR in T-47D human breast cancer cells. Cells were treated with the progestin ORG 2058 and PR mRNA measured by Northern blot analysis of total RNA. A major PR mRNA around 13.5 kilobases and minor species around the 28S ribosomal RNA subunit were decreased upon ORG 2058 treatment. The decrease was not detectable until 2-3 h after treatment and was the same at all ORG 2058 concentrations (1-100 nM) tested. The decrease in PR mRNA was unaffected by actinomycin D in the first 3 h but was inhibited thereafter. There was a partial recovery of PR mRNA levels 24 h after ORG 2058 exposure. Immunoblot analysis showed that immunoreactive PR decreased in parallel with PR mRNA. The rate of protein loss in the first 12 h after progestin treatment was related to the ORG 2058 concentration used. Nuclear run-on experiments showed that ORG 2058 caused a decrease of up to 70% in the transcription rate of the PR gene. The half-life of PR mRNA was shown to be 2-2.5 h by [3H]uridine incorporation, which was much shorter than estimates obtained using actinomycin D, and was unaffected by ORG 2058. In summary, these data have shown that the mechanism by which progestins decrease the concentration of PR includes inhibition of transcription of the PR gene.

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  1. John F. Wilber, M.D., Scientific Program Director Lectures, workshops and clinical management sessions by world-recognized experts will offer an in-depth, state of the art, review of the diagnosis and management of all major areas of contemporary endocrinology. Interrelationships between the practice of endocri- nology and developments in basic science, particularly in molecular biology, will be empha- sized. Highlights of the 1989 program will be: Computer management of diabetes Obesity Neuroradiology Nephrolithiasis Polycystic ovary syndrome Clinical management sessions Who should attend... ? Candidates for the ABIM subspecialty examination Practicing internists Intemist-Endocrinologists Endocrinologists who want the highest quality update in a fast-breaking area of medical knowledge Program and registration information will be available in June. To be placed on the mailing list, contact The Endocrine Society, 9650 Rockville Pike, Bethesda, MD 20814, 301-571- 1802, fax: 301-571-1869.

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Authors
Alexander, I. E., Clarke, C. L., Shine, J., & Sutherland, R. L.
Affiliations
Garvan Institute of Medical Research (AU)
Venue
Molecular Endocrinology
Published
1989-09
Volume
3
Issue
9
Pages
1377-1386
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
OpenAlex
W1984784419
Cited by
109
References
42
Citations by year
2020: 3 · 2019: 3 · 2018: 2 · 2012: 2
FWCI
6.38
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Keywords
progestins, progesterone receptor, gene transcription inhibition, ORG 2058, T47D cells, actinomycin D, nuclear run-on assay, breast cancer
MeSH terms
Breast Neoplasms, Cell Line, Dactinomycin, Electrophoresis, Agar Gel, Electrophoresis, Polyacrylamide Gel, Humans, Pregnenediones, Receptors, Progesterone, RNA, Messenger, Transcription, Genetic, Blotting, Northern, Down-Regulation, Gene Expression, Progesterone Congeners

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