p53 mutations and tetraploids under r- and K-selection.
Cotransfection of rat embryo fibroblasts with c-myc and activated H-ras oncogenes is one experimental model of the multistep oncogenesis associated with p53 mutations and aneuploidy. Using the model, we found that selection processes, e.g., r- and K-selection, affect emergence of p53 mutants and tetraploids. Culture optimum for logarithmic growth (r-selection) selected p53 mutants as they proliferated rapidly, while in confluent culture (K-selection) tetraploids emerged regardless of the p53 status. Transfection of the mutated p53 gene with dominant negative functions eradicated untransfected cells under both r- and K-selection. However, these p53 mutants can be eradicated under K-selection by cells with normal p53 function and that had been selected under prolonged K-selection. The presence of competitors and the type of selection should determine whether or not p53 mutants and/or tetraploids predominate. These observations strengthen the importance of selection processes in case of cancer.
Chikatsu
Norio
N
Department of Internal Medicine, Faculty of Medicine, the University of Tokyo, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112-8688, Japan.
Nakamura
Yukari
Y
Sato
Hiroyuki
H
Fujita
Toshiro
T
Asano
Shigetaka
S
Motokura
Toru
T
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D009154:Mutation; D011123:Polyploidy; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012641:Selection, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)