Treatment with bisphenol A and methoxychlor results in the growth of             human breast cancer cells and alteration of the expression of cell cycle-related             genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway.
Various endocrine disrupting chemicals (EDCs) are exogenous compounds found             in the environment and have the potential to interfere with the endocrine system             and hormonal regulation. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane             [methoxychlor (MXC)] have estrogenic activity resulting in a variety of dysfunctions             in the E2-mediated response by binding to estrogen receptors (ERs), causing human             health problems such as abnormal reproduction and carcinogenesis. In this study,             we investigated the effects of BPA and MXC on cell proliferation facilitated by             ER signaling in human breast cancer cells. MCF-7 cells are known to be ERα-positive             and to be a highly E2-responsive cancer cell line; these cells are, therefore,             a useful in vitro model for detecting estrogenic activity in response to EDCs.             We evaluated cancer cell proliferation following BPA and MXC treatment using an             MTT assay. We analyzed alterations in the expression of genes associated with             the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following             treatment with BPA or MXC compared to EtOH. To determine whether BPA and MXC stimulate             cancer cell growth though ER signaling, we co-treated the cells with agonists             (propyl pyrazoletriol, PPT; and diarylpropionitrile, DPN) or an antagonist (ICI             182,780) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells             before treatment with EDCs. These studies confirmed the carcinogenicity of EDCs             in vitro. As a result, BPA and MXC induced the cancer cell proliferation by the             upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative             genes, especially ones affecting the G1/S transition via ERα signaling. These             collective results confirm the carcinogenicity of these EDCs in vitro. Further             studies are required to determine whether EDCs promote carcinogenesis in vivo.
Laboratory of Veterinary Biochemistry and Immunology, College                     of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk                     361-763, Republic of Korea.
Hye-Rim
HR
Lee
Kyung-A
KA
Hwang
Min-Ah
MA
Park
Bo-Rim
BR
Yi
Eui-Bae
EB
Jeung
Kyung-Chul
KC
Choi
D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018816:Genes, cdc / Q000187:drug effects*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008731:Methoxychlor / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002273:Carcinogens; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D007306:Insecticides; D008731:Methoxychlor; D010636:Phenols; C493956:CDKN1A protein, human; C506487:ESR1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds