Cadmium-Induced Transcription by NFATc2 in Breast Cancer Cells

Although breast cancer is the second leading cause of cancer death among women in the United States, many of the mechanisms behind breast cancer development are unknown. It is known, however, that mis-regulated gene expression contributes to cancer development. Gene expression is tightly regulated at transcriptional initiation both by the formation of the pre-initiation complex and assembly of a host of other transcription factors, which act to promote expression of specific genes. NFATc2 is one such transcription factor implicated in breast cancer progression. This protein is regulated by intracellular calcium levels that may be induced by exposure to the environmental carcinogen, cadmium. This project aims to understand how exposure to cadmium may promote breast cancer cell invasiveness and proliferation via the NFATc2 transcription factor. MDA-MB-231 breast cancer cells exposed to 9 µM cadmium chloride (CdCl2) showed increased expression of some NFATc2-regulated genes, specifically COX-2 and IL-8. This response was shown to be cell type specific. Preliminary knockdown of NFATc2 by siRNAs show NFATc2 dependence for the cadmium-induced increase in COX-2 and IL-8 transcription. Cadmium may induce transcription of many genes regulated by NFATc2 that are important to breast cancer progression and invasiveness, which further experiments need to address