PGR and endometrial cancer: Since P4 attenuates E2 regulation of proliferation and gene expression by regulating the expression of a yet to be identified paracrine signal from the stromal cells to the epithelial cells, the regulation of the expression of ERα and PR in the endometrial stroma and epithelium by Pten ablation and the oncogenic K-ras mutation is critical for the expression of ER target genes and the tumorigenesis of endometrial cancer.