Abstract | INTRODUCTION:
Estrogen and androgen signalling pathways exert opposing influences on the proliferation of mammary epithelial and hormone-dependent breast cancer cells. We previously reported that plasma concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene ( p,p'-DDE), the main metabolite of the insecticide DDT (1,1,1-trichloro-2,2-bis [p-chlorophenyl] ethane) and a potent androgen antagonist, were associated with tumor aggressiveness in women diagnosed with breast cancer. We sought to examine the biological plausibility of this association by testing the effect of p,p'-DDE on the proliferation of CAMA-1 cells, a human breast cancer cell line that expresses the estrogen receptor alpha ( ERalpha) and the androgen receptor (AR), in the presence of physiological concentrations of estrogens and androgens in the cell culture medium. METHODS: The proliferation of CAMA-1 cells was determined in 96-well plates following a 9-day treatment with p,p'-DDE alone (0.1 to 10 muM) or in combination with 17beta-estradiol (E2) (100 pM) and dihydrotestosterone (DHT) (100, 500, or 1,000 pM). We also assessed p,p'-DDE-induced modifications in cell cycle entry and the expression of the sex- steroid-dependent genes ESR1, AR, CCND1, and TFF1 (pS2) ( mRNA and/or protein). RESULTS: We found that treatment with p,p'-DDE induced a dose-response increase in the proliferation of CAMA-1 cells when cultivated in the presence of physiological concentrations of estrogens and androgens, but not in the absence of sex steroids in the cell culture medium. A similar effect of p,p'-DDE was noted on the proliferation of MCF7-AR1 cells, an estrogen-responsive cell line that was genetically engineered to overexpress the AR. DHT added together with E2 to the cell culture medium decreased the recruitment of CAMA-1 cells in the S phase and the expression of ESR1 and CCND1 by comparison with cells treated with E2 alone. These androgen-mediated effects were blocked with similar efficacy by p,p'-DDE and the potent antiandrogen hydroxyflutamide. CONCLUSION:
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Authors | Michel Aubé, Christian Larochelle, Pierre Ayotte |
Journal | Breast cancer research : BCR
(Breast Cancer Res)
Vol. 10
Issue 1
Pg. R16
( 2008)
ISSN: 1465-542X [Electronic] England |
PMID | 18275596
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Estrogen Receptor alpha
- Insecticides
- Receptors, Androgen
- Dichlorodiphenyl Dichloroethylene
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Topics |
- Breast Neoplasms
(metabolism)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
(drug effects)
- Dichlorodiphenyl Dichloroethylene
(pharmacology)
- Estrogen Receptor alpha
(biosynthesis)
- Female
- Humans
- Insecticides
(pharmacology)
- Receptors, Androgen
(biosynthesis)
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