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The proliferative effects of 5-androstene-3β,17β-diol and 5α-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines

Lookup NU author(s): Seb Aspinall, Susan Stamp, Andrew Davison, Dr Brian Shenton, Professor Thomas Lennard

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Abstract

Epidemiological studies suggest that precursor steroids are implicated in the aetiology of breast cancer. However, our understanding of the role of precursor steroids in breast cancer is complicated by fact that there are many precursor steroids, which are metabolically inter-related and have divergent proliferative activities on the growth of breast cancer cell lines. In this study the proliferative affects of 5α-dihydrotestosterone and 5-androstene-3β,17β-diol, which may be considered true metabolites acting at a tissue level, on MCF7, T47D and MDAMB231 breast cancer cell lines have been examined by a flow cytometric technique. DNA cell cycle analysis demonstrates that 5-androstene-3β,17β-diol stimulates the proliferation of hormone-dependent cell lines at physiological levels by an oestrogen receptor mediated mechanism whereas 5α-dihydrotestosterone does not affect the proliferation of MCF7 and T47D cell lines at physiological levels over short (48h) incubations. Both 5α-dihydrotestosterone and 5-androstene-3β,17β-diol stimulate proliferation of hormone-dependent cell lines at pharmacological levels via and interaction with the oestrogen receptor. In long (6-9 days) incubations both 5α-dihydrotestosterone and 5-androstene-3β,17β-diol inhibit the 17β-oestradiol induced proliferation of MCF7 and T47D cell lines, however, 5α- dihydrotestosterone inhibits while 5-androstene-3β,17β-diol stimulates basal proliferation. These cell line studies suggest a model for the role of precursor steroids in pre- and postmenopausal breast cancer. © 2004 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Aspinall, S., Stamp, S., Davison, A., Shenton, B.K., Lennard, T.W.J.

Publication type: Article

Publication status: Published

Journal: Journal of Steroid Biochemistry and Molecular Biology

Year: 2004

Volume: 88

Issue: 1

Pages: 37-51

Print publication date: 01/01/2004

ISSN (print): 0960-0760

ISSN (electronic): 1879-1220

URL: http://dx.doi.org/10.1016/j.jsbmb.2003.10.011

DOI: 10.1016/j.jsbmb.2003.10.011

PubMed id: 15026082


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