CADMIUM PROMOTES PROLIFERATION OF TRIPLE-NEGATIVE BREAST CANCER CELLS THROUGH EGFR-MEDIATED CELL CYCLE REGULATION

Abstract

Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer by epidemiological studies. In cell culture studies, it is reported to promote breast cancer cell growth through membrane estrogen receptors. Triple-negative breast cancer patients are non-responsive to endocrine and trastuzumab therapy and have the worst prognosis and lowest survival rate. The purpose of this study was to examine whether Cd can promote the growth of non-metastatic, triple-negative human breast cancer cells HCC 1937, which are positive for epidermal growth factor receptor (EGFR). It was found that Cd treatment (0.1-0.5 μM) promoted cell growth and accelerated cell cycle progression by increasing cyclins A, B, and E, and CDK 1, and 2 expressions. Further study using kinase inhibitors indicated that MAPK and PI3K activation was required for this process. The kinase activation in turn was mediated through EGFR activation. Based on these findings, it is concluded that sub-micromolar concentration of Cd induces proliferation of HCC 1937 cells through EGFR, MAPK and PI3K regulated cell cycle progression. The involvement of EGFR in Cd-stimulated early stage and triple-negative breast cancer cell growth implicates Cd’s role in breast cancer progression. Keywords: Cadmium, Breast Cancer, Cell Proliferation, Cell Cycle, EGFR