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Cadmium‐induces Cell Cycle Progression in Triple‐negative Breast Cancer Cells Through EGFR
Author(s) -
Wei Zhengxi,
Song Xiulong,
Shaikh Zahir
Publication year - 2015
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.29.1_supplement.934.6
Subject(s) - cyclin dependent kinase , cancer research , cell cycle , cdk inhibitor , protein kinase b , cell growth , chemistry , egfr inhibitors , cyclin , breast cancer , phosphorylation , pi3k/akt/mtor pathway , cancer , epidermal growth factor receptor , biology , microbiology and biotechnology , medicine , signal transduction , biochemistry
Cadmium (Cd), a known endocrine disruptor, has been shown to promote the growth of estrogen receptor positive breast cancer cells. The objective of this study was to investigate whether Cd can also promote the growth of triple‐negative breast cancer cells, and if so, whether it is mediated by EGFR. Human breast cancer HCC 1937 cells were treated with 0.05–1 µM CdCl 2 . Cell proliferation was assessed by MTT assay, cell cycle analysis and expression of cyclins and CDKs. EGFR's role in Cd‐induced cell cycle progression was studied by siRNA knockdown and inhibition of phosphorylation of EGFR and its downstream targets. The results showed that indeed Cd treatment promoted HCC 1937 cell cycle progression and it did so by increasing the levels of cyclins A, B and E, and CDKs 1 and 2. The cell cycle progression was suppressed by EGFR inhibitor AG1478. Cd treatment caused phosphorylation of EGFR and its downstream targets, Src, AKT and ERK1/2. Both EGFR siRNA and EGFR inhibitor decreased the phosphorylation of ERK1/2. Furthermore, inhibitors of ERK1/2 and AKT phosphorylation decreased the Cd‐induced expression of cyclins and CDKs. Based on these results, it is concluded that low concentrations of Cd induce proliferation of HCC 1937 cells through EGFR‐mediated cell cycle progression. This study provides a novel mechanism by which Cd promotes cell growth in triple‐negative breast cancer cells.