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 p27KIP1. This has been attributed to reduced apoptosis and weakening of the G1 checkpoint. However, the role of p27KIP1 in a recently identified G2 restriction point may offer an alternative explanation for this synergy. Here, we have investigated the significance of the G2 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 B1-p27KIP1 complexes. Somewhat unexpectedly, these complexes remained present in Rb-deficient tumors. These results indicate that the G2 restriction point does operate in vivo. However, in the pituitary gland, this mechanism seems to retard rather than to prevent tumor growth.
Foijer
Floris
F
Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Delzenne-Goette
Elly
E
Dekker
Marleen
M
Te Riele
Hein
H
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics*; D051379:Mice; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; C493961:Cdkn1b protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27