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Chronic cadmium exposure reduces the dependence of MCF7 cells on ERa for cell growth
Author(s) -
Bloomfield Mathew,
Louie Maggie
Publication year - 2018
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.2018.32.1_supplement.678.5
Subject(s) - breast cancer , cadmium , cancer research , cancer , cancer cell , cell growth , biology , estrogen receptor , medicine , endocrinology , immunology , chemistry , genetics , organic chemistry
The global prevalence of breast cancer in women illustrates the importance of identifying factors that contribute to disease onset and progression. Endogenous and environmental agents that interact with estrogen receptor alpha (ERa) have been shown to play a role in breast cancer etiology. Evidence from epidemiological studies and animal models have suggested that cadmium, a heavy metal that can activate ERa, contributes to the development and progression of breast cancer. Additionally, our lab showed that chronic cadmium exposure altered the expression of several ERa‐responsive genes and increased the malignancy of MCF7 breast cancer cells. Although these studies support cadmium's function as a hormone disrupter, the role of ERa in cadmium‐induced breast cancer progression remains unclear. Therefore, we modulated the expression of ERa in MCF7 cells after chronic cadmium exposure (Cd7 and Cd12) in order to understand its role in cadmium‐induced cancer cell growth and gene expression. The doubling times of MCF7, Cd7, and Cd12 cells were increased as a result of ERa loss, but this effect was significantly less in the cadmium‐adapted cells suggesting chronic cadmium exposure reduces the dependence of MCF7 cells on ERa for cell growth. Furthermore, preliminary analysis showed the transcript levels of classical and non‐classical ERa‐regulated genes were reduced in MCF7 cells after transient and permanent modification of ERa expression, while the non‐classical targets were not as affected in Cd7 and Cd12 cells after ERa knockout indicating cadmium exposure may have altered the regulation of these genes. These results demonstrate that while ERa still contributes to the growth of MCF7 cells chronically exposed to cadmium, their dependency on ERa appears to have diminished. The relevant processes affected by chronic cadmium exposure remain unclear, but these may enable MCF7 cells to adapt to ERa loss and potentially provide a path to ERa independence as the cancer progresses. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .