Cadmium Induced Transcription and NFAT/cJun Proximal Promoter Binding in Breast Cancer Cells

In order to better comprehend onset and progression of diseases such as cancer, the means by which genes are regulated must be understood. RNA Polymerase II (Pol II) transcribes mRNAs that are translated into proteins, but this process is tightly controlled by transcription factors that recruit Pol II to promoter elements. These transcription factors determine if and when a gene is expressed at a basal level. This thesis focuses on the NFAT and AP-1 family of transcription activators. Each of these families has been characterized as important transcriptional activators in the onset and growth of cancer, but their mechanism of action is not well understood. Genes up-regulated in mammary duct carcinoma in response to the environmental carcinogen cadmium chloride were identified. These genes where then used to determine the optimal cadmium concentration and time of treatment for maximal transcriptional induction. ChIP assays against NFATc2 and cJun were performed before and after treatment with cadmium. ChIP and qRT-PCR data collected suggests that genes MMP-1 and RAB11 are upregulated via cadmium chloride exposure and transcription factors NFATc2 and AP-1 are bound to promoter elements of each of these genes.