FoxA supports breast cancer growth by regulating LIPG transcription and lipid metabolism

The mechanisms that allow breast cancer cells to metabolically sustain growth are poorly understood. In breast cancer, FoxA1 transcription factor, along with estrogen receptor, regulates luminal cell specification and proliferation. Here we report that FoxA transcription factor family members FoxA1 and FoxA2 fuel cellular growth in breast cancer through the expression of a common target gene, namely the endothelial lipase (LIPG) We used microarrays to detail the genes that are under de control of FoxA transcription factors in MDA231 and MCF7 breast cancer cells Isolated Breast cancer cells derived from non-depleted (Dox−) FoxA1 or FoxA2 MCF7 and MDA231 tumors (control groups), FoxA1- and FoxA2-depleted MCF7 and MDA231 tumors (knockdown groups) and the corresponding FoxA family-rescued tumors (rescued group) subjected to transcriptomic analysis using a GeneAtlas Human Genome U-219 Affymetrix array. Genes regulated by FoxA1 and FoxA2 were selected on the basis of the following criteria: (1) decreased expression in MCF7 and MDA231 cells upon FoxA depletion compared to control cells; and (2) increased expression in MCF7 and MDA231 FoxA-rescued cells compared to the respective FoxA-depleted population; or (1) increased expression in MCF7 and MDA231 cells upon FoxA depletion compared to control cells; and (2) decreased expression in MCF7 and MDA231 FoxA-rescued cells compared to the respective FoxA-depleted population.