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The endocrine disruptors cadmium chloride and sodium arsenate induce human lung adenocarcinoma cell proliferation by activating the estrogen receptor‐mediated signaling pathway
Author(s) -
Murphy Robert D.,
Smith Aaron L.,
Todd Sarah L.,
Elpers Julia T.,
Radde Brandie N.,
Klinge Carolyn M.,
Huff Mary O.
Publication year - 2012
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.26.1_supplement.765.3
Subject(s) - cadmium chloride , sodium arsenate , estrogen receptor , chemistry , endocrinology , kinase , medicine , cancer research , cadmium , biology , biochemistry , arsenate , cancer , arsenic , breast cancer , organic chemistry
Estrogens have been implemented in non‐small cell lung cancer (NSCLC) risk, but the contribution and possible mechanisms of the endocrine disruptors cadmium chloride and sodium arsenate have not been delineated. Previous studies indicate that 17β‐estradiol (E 2 ) induces lung cancer cell proliferation through activation of EGFR, Src‐kinase, MEK1 and ERK1/2. The purpose of this study is to determine if cadmium chloride and sodium arsenate stimulate NSCLC growth using a similar mechanism. Treatment of human lung adenocarcinoma NCI‐H1793 cells with nanomolar concentrations of these endocrine disruptors stimulate proliferation in a manner similar to E 2 , and proliferation is reduced when cells were first treated with the estrogen receptor (ER) antagonist ICI 182,780. Further, cadmium chloride and sodium arsenate, like E 2 , stimulate phosphorylation of ERK1/2 (pERK1/2) within 15 min of treatment, and pERK1/2 is reduced by ICI 182,780 suggesting that activation is mediated through ER. Studies using the MEK1 antagonist PD98059, the Src‐kinase antagonist PP2 and the EGFR antagonist Tyrphostin‐AG1478 indicate that MEK1, Src‐kinase and EGFR activation is required for the cadmium chloride‐ and sodium arsenate‐ induced increase in pERK1/2. These results support the involvement of membrane‐ ER signaling in mediating cellular responses to cadmium chloride and sodium arsenate in human lung adenocarcinoma cells.