The aim of this study was to explore the effect of bisphenol A (BPA) on the EGFR-STAT3 pathway in breast cancer. We applied 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay to the analysis of the responsiveness of MCF-7 cells to BPA. Gene expression was assayed at the transcriptional and translational levels by reverse transcription-PCR and Western blotting. We explored the effects of BPA on MCF-7 cell proliferation through inhibition of the related genes, STAT3, using RNA interference, and EGFR, using its inhibitor AG1478. The optimal concentration and time point of BPA-induced proliferation in MCF-7 cells are 1 mu M and 24 h, respectively. BPA significantly increased the expression of STAT3 at a concentration of 1 mu M following treatment for 48 h and the expression of STAT3 was down-regulated after blocking EGFR. When STAT3 was blocked in MCF-7 cells, BPA did not appear to induce cell proliferation. Treatment with BPA (1 mu M) in the presence of AG1478 for 48 h resulted in the stimulation of cell growth in MCF-7 cells, similar to that of the BPA alone treatment. BPA increases STAT3 expression, which is a major factor in the pathway of BPA-induced proliferation, and STAT3 activation contributes to BPA-induced breast cancer cell proliferation. However, EGFR mediates negative signaling for BPA-induced breast cancer cell proliferation.
[1]Jilin Univ, Res Ctr, Clin Hosp 1, Changchun 130021, Jilin, Peoples R China.
[2]Jilin Prov Hosp, Dept Tumor Biol Therapy, Changchun 130021, Jilin, Peoples R China.
[3]Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, Div Hematol Oncol, New York, NY USA.
[4]Jilin Univ, China Japan Union Hosp, Dept Orthopaed, Changchun 130033, Jilin, Peoples R China.
[5]Jilin Univ, Clin Hosp 1, Virus & AIDS Res Ctr, Changchun 130021, Jilin, Peoples R China.
[6]Jilin Univ, Coll Nursing, Dept Obstet & Gynecol, Changchun 130021, Jilin, Peoples R China.
(8.0+极速模式)