The murine gene p27Kip1 is haplo-insufficient for tumour suppression

摘要: p27Kip is a candidate human tumour-suppressor protein, because it able to inhibit cyclin-dependent kinases and block cell proliferation. Abnormally low levels of the p27 protein are frequently found in carcinomas, these correlate directly with both histological aggressiveness patient mortality. However, has not been possible establish causal link between tumour suppression, only rare instances homozygous inactivating mutations gene have tumours. Thus, p27Kip1 does fulfil Knudson's 'two-mutation' criterion for gene. Here we show that nullizygous heterozygous mice predisposed tumours multiple tissues when challenged gamma-irradiation or chemical carcinogen. Therefore multiple-tissue suppressor mice. Molecular analyses remaining wild-type allele neither mutated nor silenced. Hence, haplo-insufficient suppression. The assumption null genes recessive excludes those exhibit haplo-insufficiency.