Figure 8

Schematic illustration of molecular pathway initiated by P4 signaling in BPBC cells. MB468 cells usually maintain the activities of PI3K/Akt at high levels because these cells contain a mutant pten gene and over expressed epidermal growth factor receptor (EGFR). Activation of PI3K/Akt pathway is a vital signal for cell survival and epithelial to mesenchymal transition (EMT). It is assumed that the binding of progesterone (P4) to membrane progesterone receptor (mPR) α in the caveolar membrane of the cells inhibits EMT-relevant events either directly through Caveolar (Cav) 1 activation or through a cross interaction with EGFR and trans-activation of Cav-1 which subsequently inactivate PI3K/Akt pathway. Inactivation of PI3K/Akt pathway subsequently inhibits the nuclear translocation of snail and then modulates expression of other EMT-relevant proteins.