ABSENCE OF P53 ALLOWS DIRECT IMMORTALIZATION OF HEMATOPOIETIC-CELLS BY THE MYC AND RAF ONCOGENES

The p53 tumor suppressor is implicated here as a crucial barrier to unlimited cell proliferation. Its role in transformation of hematopoietic cells was studied by infecting fetal liver cells from wild-type or p53(-/-) mice with oncogenic retroviruses. Transformed colonies arose with a raf and a myc-raf virus. Absence of p53 did not affect their frequency but proved critical for their continued propagation. Colonies of p53(-/-) cells bearing both myc and raf readily yielded continuous cell lines without apparent requirement for genetic alteration. The lines, mainly of erythroid or myelomonocytic origin, were diploid but highly tumorigenic from their inception. These findings imply that p53 loss contributes directly to immortalization and tumorigenesis, probably by abrogating an intrinsic senescence program.