Cadmium Promotes Breast Cancer Cell Proliferation by Potentiating the Interaction between ERα and c-Jun

Cadmium is an environmental contaminant that enters the body through diet or cigarette smoke. It affects multiple cellular processes, including cell proliferation, differentiation, and apoptosis. Recently, cadmium has been shown to function as an endocrine disruptor, to stimulate estrogen receptor alpha (ER alpha) activity and promote uterine and mammary gland growth in mice. Although cadmium exposure has been associated with the development of breast cancer, the mechanism of action of cadmium remains unclear. To address this deficit, we examined the effects of cadmium treatment on breast cancer cells. We found that ER alpha is required for both cadmium-induced cell growth and modulation of gene expression. We also determined that ER alpha translocates to the nucleus in response to cadmium exposure. Additionally, we provide evidence that cadmium potentiates the interaction between ER alpha and c-Jun and enhances recruitment of this transcription factor complex to the proximal promoters of cyclin D1 and c-myc, thus increasing their expression. This study provides a mechanistic link between cadmium exposure and ER alpha and demonstrates that cadmium plays an important role in the promotion of breast cancer. (Molecular Endocrinology 24: 981-992, 2010)