p16INK4a and p53 deficiency cooperate in tumorigenesis

Norman E. Sharpless, Scott Alson, Suzanne Chan, Daniel P. Silver, Diego H. Castrillon, Ronald A. DePinho

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


The combined impact of mutations in p16INK4a and p53 was examined in cellular growth, transformation, and tumor formation. In cultured cells, p16INK4a loss enhanced growth at high density and conferred susceptibility to oncogene-induced transformation. In vivo, mice doubly deficient for p16INK4a and p53 showed an increased rate of tumor formation with particular susceptibility to aggressive angiosarcomas. Furthermore, p16INK4a silencing by promoter methylation was detected in tumors derived from p16INK4a+/- and+/+ mice, independent of p53 status. These data suggest at least one general feature of malignancy, resistance to density-mediated growth arrest depends on p16INK4a rather than p53. This cooperation between p16INK4a and p53 loss in tumorigenesis is consistent with the view that these genes function in distinct anticancer pathways.

Original languageEnglish (US)
Pages (from-to)2761-2765
Number of pages5
JournalCancer research
Issue number10
StatePublished - May 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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