A NOVEL CANDIDATE TUMOR-SUPPRESSOR, ING1, IS INVOLVED IN THE REGULATION OF APOPTOSIS

We have recently cloned a novel growth inhibitor and candidate tumor s uppressor called p33(ING1) (I. Garkavtsev et al., Nature Genet,, 14: 4 15-420, 1996), Because some tumor suppressors participate in the regul ation of apoptosis, we hypothesized that the ING1 gene may also play a role in this process, Our results show that p33(ING1) levels increase upon the induction of apoptosis in P19 teratocarcinoma cells by serum deprivation, Elevated expression of ING1 in P19 and rodent fibroblast cells containing a tetracycline-controlled human c-myc gene enhanced the extent of serum starvation-induced apoptosis, This suggests that t he pathway by which ING1 modulates cell death is synergistic with Myc- dependent apoptosis, Conversely, constitutive expression of an antisen se construct of ING1 conferred protection against apoptosis in these c ells, These data support the idea that loss of proper ING1 function ma y facilitate tumorigenesis, in part, by reducing the cell's sensitivit y to apoptosis.