Search resultsAlcohol stimulates estrogen receptor signaling in human breast cancer cell lines
Title
Alcohol stimulates estrogen receptor signaling in human breast cancer cell lines
Publication type
Journal Article
Year of Publication
2000
Authors
Journal
Cancer Research
Volume
60
Issue
20
Pagination
5635 - 5639
Date published
2000
ISBN
00085472 (ISSN)
Keywords
alcohol, alcohol blood level, alcohol consumption, article, BRCA1 protein, breast carcinogenesis, breast carcinoma, Breast Neoplasms, cancer cell culture, cancer risk, controlled study, Dose-Response Relationship, Drug, Down-Regulation, estrogen receptor alpha, estrogen therapy, Ethanol, expression vector, Gene Expression Regulation, Neoplastic, Genes, BRCA1, human, human cell, Humans, Neoplasms, Hormone-Dependent, priority journal, Receptors, Estrogen, signal transduction, Trans-Activation (Genetics), Tumor Cells, Cultured
Abstract
Epidemiological studies suggest that moderate alcohol consumption increases the risk of breast cancer, and that alcohol combined with estrogen replacement therapy may synergistically enhance the risk. However, the mechanism(s) of alcohol-induced mammary cancer is unknown. In human breast cancer cell lines, we found that ethanol (EtOH) caused a dose-dependent increase of up to 10- to 15-fold in the transcriptional activity of the liganded estrogen receptor (ER-α), but did not activate the nonliganded receptor. Significant stimulation of ER-α activity was observed at EtOH concentrations comparable with or less than blood alcohol levels associated with intoxication and at doses below the threshold for in vitro cytotoxicity. These findings may be explained, in part, by an EtOH-induced down-regulation of the expression of BRCA1, a potent inhibitor of ER-α activity, and, in part, by a modest increase in the ER-α levels. Our findings suggest that inactivation of BRCA1 and increased estrogen-responsiveness might contribute to alcohol-induced breast cancer.