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Androgen-Induced Inhibition of Proliferation in Human Breast Cancer MCF7 Cells Transfected with Androgen Receptor*
- Source :
- Endocrinology. 138:1406-1412
- Publication Year :
- 1997
- Publisher :
- The Endocrine Society, 1997.
-
Abstract
- Sex steroids control the proliferation of their target cells through two different pathways: 1) proliferative response (Step-1); and 2) inhibition of cell proliferation (Step-2). Mechanisms of cell proliferation regulation are incompletely understood; however, there is general agreement with the notion that sex steroid receptors play an important role in the control of the proliferation of sex steroid target cells. To test this hypothesis, a full human androgen receptor (AR) vector was transfected into human breast cancer MCF7 cells. The cloned cells that stably express the AR, called MCF7-AR1 cells, contained approximately five times more AR than the wild-type MCF7 cells from which they were derived. These AR-transfected cells retained their capacity to proliferate when estrogens were added to 10% charcoal-dextran stripped human serum but did not acquire the ability to proliferate when androgens were added to this medium. In serumless medium (ITDME), these cells proliferated maximally, as MCF7 cells did; however, natural and synthetic androgens prevented the AR-transfected cells from proliferating. Inhibition of cell proliferation occurred when physiological androgen concentrations (1 nM) were added to ITDME; this effect was almost completely reversed by Casodex, a synthetic androgen antagonist. Under the effect of androgens added to ITDME, MCF7-AR1 cells were arrested in the G0/G1 phase within 24 h. These data suggest that: 1) the androgen-induced inhibition of cell proliferation (Step-2) is AR-mediated; and 2) the AR may be necessary, but not sufficient, to mediate the androgen-induced proliferative response (Step-1).
- Subjects :
- medicine.medical_specialty
medicine.drug_class
Blotting, Western
Breast Neoplasms
In Vitro Techniques
Biology
Transfection
Tosyl Compounds
Endocrinology
Breast cancer
Internal medicine
Nitriles
Tumor Cells, Cultured
medicine
Humans
Nandrolone
Anilides
Testosterone
Testosterone Congeners
Dose-Response Relationship, Drug
Cell growth
Cell Cycle
Cancer
Androgen Antagonists
Dihydrotestosterone
Sex hormone receptor
Metribolone
Androgen
medicine.disease
Flutamide
Androgen receptor
Receptors, Androgen
Sex steroid
Androgens
Female
Cell Division
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....4ceaa21e347f15135eaf9a2bc1f105f2