title: Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.
abstract: Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point.
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mazel
authors.forename: D
authors.initials: D
authors.lastname: Burtrum
authors.forename: H T
authors.initials: HT
authors.lastname: Petrie
mesh_terms: D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004247:DNA / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D004247:DNA; D001973:Bromodeoxyuridine