TUMOR-SUPPRESSOR P53 IS A REGULATOR OF BCL-2 AND BAX GENE-EXPRESSION IN-VITRO AND IN-VIVO

The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-s ensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M 1, while simultaneously stimulating increases in the expression of bax , a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax prot ein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by whi ch p53 regulates apoptosis, as well as responses to radiation and chem otherapeutic drugs in cancer.