Expression of the wild-type p53 antioncogene induces guanine nucleotide-dependent stem cell division kinetics.
The predominant type of cell division in adult mammals is renewal growth. Renewing stem cells in somatic tissues undergo continuous asymmetric divisions. One new daughter cell retains the division potential of the original stem cell, while the other differentiates into a functional constituent of the tissue. Disruptions of this process lead to the development of human cancers. We show that through a guanine nucleotide-dependent mechanism, the p53 antioncogene can induce exponentially dividing cells to switch to an asymmetric stem cell growth pattern. This finding suggests that the observed high frequency of p53 mutations in human cancers reflects a critical function in the regulation of somatic renewal growth.
Sherley
J L
JL
Department of Molecular Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Stadler
P B
PB
Johnson
D R
DR
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D015870:Gene Expression; D016158:Genes, p53; D006150:Guanine Nucleotides / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008322:Mammals; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D012044:Regression Analysis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D006150:Guanine Nucleotides; D016159:Tumor Suppressor Protein p53