In vivo significance of the G2 restriction point

Loss of activity of the retinoblastoma pathway is a common event in human cancer. Mouse models have revealed that tumorigenesis by loss of Rb was accelerated by concomitant loss of the cell cycle inhibitor p27(KIPI). This has been attributed to reduced apoptosis and weakening of the G(1) checkpoint. However, the role of p27(KIP1) in a recently identified G(2) restriction point may offer an alternative explanation for this synergy. Here, we have investigated the significance of the G(2) restriction point in Rb-deficient pituitaries. We show that Rb loss in the pituitary gland activated the G2 restriction point, as evidenced by the appearance of cyclin BI-p27 (KIPI) complexes. Somewhat unexpectedly, these complexes remained present in Rb-deficient tumors. These results indicate that the G(2) restriction point does operate in vivo. However, in the pituitary gland, this mechanism seems to retard rather than to prevent tumor growth.