EXTENSION OF THE REPLICATIVE LIFE-SPAN OF HUMAN-DIPLOID FIBROBLASTS BY INHIBITION OF THE P33(ING1) CANDIDATE TUMOR-SUPPRESSOR

Previous studies suggest that tumor suppressors may play significant r oles in blocking the growth of cells during cellular senescence, We th erefore studied the potential involvement of a novel growth inhibitor and candidate tumor suppressor gene called ING1, which we have cloned recently (I. Garkavtsev, A. Kazarov A. Gudkov, and K. Riabowol, Nat, G enet, 14:415-420, 1996), in the process of cellular senescence, Our re sults show that the RNA and protein levels of ING1 were 8- to 10-fold higher in senescent cells than in young, proliferation-competent human diploid fibroblasts. Expression of the nuclear p33(ING1) during the c ell cycle, reaching maximal levels during DNA synthesis, Chronic expre ssion of antisense ING1 RNA reproducibly resulted in extension of the proliferative life span of normal human fibroblasts by approximately s even population doublings.