Differential expression of estrogen receptor alpha (ERalpha) protein in MCF-7 breast cancer cells chronically exposed to TCDD.
Estrogens play a key role in the development and evolution of breast cancer tumors. Estrogen receptor alpha (ERalpha) mediates many of the biological activities of estrogens, and its expression is associated with low invasiveness and good prognosis. Recent epidemiological reports suggest that long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is implicated in the increased incidence of breast cancer in exposed women. TCDD interferes with the expression of some ERalpha-dependent genes and inhibits estradiol (E2)- dependent growth of breast cancer cells in vitro. However, E2-dependent xenographs of MCF-7 human breast cancer cells resumed growth after a 2-week exposure to TCDD. The mechanisms involved in the resumption of cell growth are not completely understood. In this study, we show that short term-exposure (16 days) to 1 nM TCDD results in the suppression of ERalpha protein expression, while chronic exposure for more than 1 year (LTDX cells) results in the partial re-expression of the receptor. Immunocytochemistry studies showed that re-expression of ERalpha in LTDX cells occurred in some of the cells. Analysis by Western immunoblots indicated that four out of five LTDX clones expressed ERalpha at levels comparable to those in unexposed MCF-7 cells. Removal of TCDD treatment for 16 days restored the expression of ERalpha in the ERalpha-negative clonal cells. These results suggest that MCF-7 cells chronically exposed to TCDD contain at least two cell subpopulations that may respond differently to the ERalpha-mediated effects of TCDD.
Marquez-Bravo
Lydia G
LG
Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, New York, USA.
Gierthy
John F
JF
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004351:Drug Resistance; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D009363:Neoplasm Proteins; D000072317:Polychlorinated Dibenzodioxins; D004958:Estradiol; D019363:Cytochrome P-450 CYP1A1