Abrogation of a kinase-mediated G1 cell cycle arrest point is a late event in the neoplastic progression of human fibroblasts transfected with the SV40 large T antigen gene.
Cell cycle arrest points that are sensitive to the kinase inhibitor staurosporine have been shown to have widely differing sensitivities for processes in G1 and G2. In addition, the exquisitely sensitive G1 arrest point has been reported to be abrogated in neoplastically transformed cells. Using a multistep model of the neoplastic process in human cells, we show here that abrogation of the G1 arrest point occurred in 5 of 11 tumorigenic cell populations. The abrogation, in those instances when it occurred, was a late step and associated with the acquisition of tumorigenicity, but apparently independent of conventional criteria for in vitro transformation.
Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545.
P M
PM
Kraemer
E M
EM
Bradbury
D000470:Alkaloids / Q000494:pharmacology; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005347:Fibroblasts; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D019311:Staurosporine; D014162:Transfection; D014410:Tumor Stem Cell Assay
D000470:Alkaloids; D000957:Antigens, Viral, Tumor; D010770:Phosphotransferases; D019311:Staurosporine