ESR1 and breast cancer: Moreover, in Erα-positive breast cancer cells, PPARγ activation, via the upregulation of PTEN, shuts down the signals of the PI3K/Akt signaling cascade, mechanistically inducing growth arrest; PPARγ-mediated transcriptional events linked to cell cycle regulation can repress cyclin D1 expression [28] and upregulate p53 protein expression and its effector p21 in breast cancer cells [24].