Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53

Malignant transformation of primary cells requires at least two distinct and characteristic alterations in cellular behaviour. The first, cellular immortality1,2, can be induced by chemical carcinogens3 or by cloned oncogenes such as polyoma large T (ref. 4), adenovirus early region 1A (E1A) or the oncogene from avian (MC29) myelocytomatosis virus, v-myc. Cells whose in vitro life-span has been extended by these procedures can be fully transformed by transfection with oncogenes belonging to a different complementation group, including genes of the ras family, adenovirus Elb and polyoma virus middle T (refs 4,5). The unstable cellular phosphoprotein p53 is frequently present at elevated levels in transformed cells6–11 and is stabilized by the formation of complexes with simian virus 40 (SV40) large T or adenovirus Elb 57K protein10–13. Although several reports have associated p53 with cell proliferation14–17, its role remains obscure. We have cloned complementary DNA sequences encoding murine p5318 and report here that transfection of p53 expression constructs into cells of finite lifespan in vitro results in cellular immortality and susceptibility to transformation by a ras oncogene.