Meta-analysis of gene expression profiling reveals novel basal gene signatures in MCF-10A cells transformed with cadmium.

Abstract

Cadmium (Cd2+) is an environmental toxicant and a human carcinogen. Several studies show an association of Cd2+ exposure to the development of breast cancer. Previously, we have transformed the immortalized non-tumorigenic cell line MCF-10A with Cd2+ and have demonstrated that the transformed cells have anchorage independent growth. In a separate study, we showed that transformation of the immortalized urothelial cells with the environmental carcinogen arsenite (As3+) results in an increase in expression of genes associated with the basal subtype of bladder cancer. In this study, we determined if transformation of the MCF-10A cells with Cd2+ would have a similar effect on the expression of basal genes. The results of our study indicate that there is a decrease in expression of genes associated with keratinization and cornification and this gene signature includes the genes associated with the basal subtype of breast cancer. An analysis of human breast cancer databases indicates an increased expression of this gene signature is associated with a positive correlation to patient survival whereas a reduced expression/absence of this gene signature is associated with poor patient survival. Thus, our study suggests that transformation of the MCF-10A cells with Cd2+ produces a decreased basal gene expression profile that correlates to patient outcome.