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Proteomic evaluation of pesticide‐resistant breast cancer cell lines
Author(s) -
Hale Julie,
Yamamoto Fiona,
Bush Jason A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb143
Subject(s) - estrogen receptor , pesticide , methoxychlor , cytotoxicity , estrogen receptor alpha , endocrine system , biology , chemistry , breast cancer , cancer research , cancer , endocrinology , biochemistry , hormone , genetics , in vitro , ecology
Considerable evidence links cumulative and sustained exposure to estrogens as a key promoter of breast tumor proliferation. Chemicals with estrogenic activity can bind to the estrogen receptor (ER) affecting signaling and estrogen‐responsive genes. Organochlorines are a class of chemical pesticides that act as xenoestrogens to disrupt normal endocrine function. Methoxychlor and Toxaphene are two organochlorine pesticides that have been widely used in California. This study investigates the response to these pesticides in an ER‐dependent manner by utilizing the breast cancer cell lines, MCF7 (ER+) and MDA‐MB‐231 (ER−), and a proteomic‐based approach to evaluate molecular pathway involvement. Cytotoxicity studies demonstrate that MCF7 cells are more sensitive to both pesticides supporting the premise that organochlorines may be acting as endocrine disruptors. Furthermore, pesticide‐resistant clones of MCF7 and MDA‐MB‐231 were established and compared to sensitive cells in proteomic experiments focused on the mitochondrial subproteome due to its role in cellular detoxification and apoptosis. We report here the elevated expression of a small subset of mitochondrial proteins in response to long‐term organochlorine exposure. These results provide a basis for understanding specific pesticide‐induced molecular mechanisms and their possible relationship to ER status in breast cancer.