H-, K- and N-Ras inhibit myeloid leukemia cell proliferation by a p21WAF1-dependent mechanism

摘要: Mutated ras genes are frequently found in human cancer. However, it has been shown that oncogenic inhibits growth of primary cells, through pathways involving p53 and the cell cycle inhibitors p16INK4a p19ARF. We have analysed effect ectopic expression three mammalian on proliferation K562 leukemia which deficient for p53, p16INK4a, p15INK4b p19ARF genes. high levels both wild-type H-, K- N-ras inhibit clonogenic cells. Induction H-rasV12 transfectants retards this is accompanied with an increase p21WAF1 mRNA protein levels. Furthermore, promoter activated potently by less pronounced ras. This induction p53-independent since a devoid responsive elements still Ras. Finally, inhibition antisense construct partially overcomes inhibitory action H-ras. Altogether, these results indicate antiproliferative myeloid cells associated to suggest existence p16INK4a-independent ras-mediated inhibition.