Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation.
Cell cycle "checkpoints" help to ensure the integrity of normal cellular functions prior to replicative DNA synthesis and/or cell division. Cell kinetic abnormalities, particularly arrests at the G1/S and G2/M cell cycle checkpoints, are induced following exposure to ionizing radiation in vitro. Following irradiation, cellular signaling pathways may lead to G1 arrest and/or apoptosis at the G1/S cell cycle transition point. Transfection of cyclin D1, a G1/S cyclin, into a rat embryo cells (REC) results in cellular populations that overexpress cyclin D1, are transformed morphologically, demonstrate an increased incidence of apoptosis, and are tumorigenic in immune-deficient mice. Despite such phenotypic changes, transfected cell populations maintain the integrity of the G1 checkpoint following ionizing radiation. The transfected cells overexpressing Cyclin D1 have a statistically significant increase in the incidence of apoptosis as compared to parental REC strains or mock-transfected REC. The work provides further evidence of Cyclin D1 playing a critical role in maintaining the integrity of the G1/S checkpoint, via the activation of apoptotic pathways following exposure to ionizing radiation in vitro.
Pardo
F S
FS
Laboratory of Molecular/Tumor Radiation Biology Mass Gen. Hosp./Harvard Medical School, Boston, USA.
Su
M
M
Borek
C
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D016213:Cyclins / Q000096:biosynthesis / Q000502:physiology*; D004622:Embryo, Mammalian; D016193:G1 Phase / Q000528:radiation effects*; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D051381:Rats; D011916:Rats, Inbred F344; D016196:S Phase; D014162:Transfection
D016213:Cyclins