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 language||English (US)|
|Number of pages||5|
|Publication status||Published - May 15 2002|
ASJC Scopus subject areas
- Cancer Research