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Lookup NU author(s): Seb Aspinall,
Dr Brian Shenton,
Professor Thomas Lennard
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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.
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
Print publication date: 01/01/2004
ISSN (print): 0960-0760
ISSN (electronic): 1879-1220
PubMed id: 15026082
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