The proliferative effects of 5-androstene-3 beta,17 beta-diol and 5 alpha-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines.
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 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-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-3 beta,17 beta-diol stimulates the proliferation of hormone-dependent cell lines at physiological levels by an oestrogen receptor mediated mechanism whereas 5 alpha-dihydrotestosterone does not affect the proliferation of MCF7 and T47D cell lines at physiological levels over short (48 h) incubations. Both 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-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 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol inhibit the 17 beta-oestradiol induced proliferation of MCF7 and T47D cell lines, however, 5 alpha-dihydrotestosterone inhibits while 5-androstene-3 beta,17 beta-diol stimulates basal proliferation. These cell line studies suggest a model for the role of precursor steroids in pre- and postmenopausal breast cancer.
Aspinall
S R
SR
School of Surgery and Reproductive Sciences, The Medical School, University of Newcastle, Newcastle upon Tyne, Benton NE2 4HH, UK. sebaspinall@tiscali.co.it
Stamp
S
S
Davison
A
A
Shenton
B K
BK
Lennard
T W J
TW
D045930:Anabolic Agents / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology; D015114:Androstenediol / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D013997:Time Factors
D045930:Anabolic Agents; D000728:Androgens; D013196:Dihydrotestosterone; D015114:Androstenediol