MICROINJECTION OF MONOCLONAL-ANTIBODY PAB421 INTO HUMAN SW480 COLORECTAL-CARCINOMA CELLS RESTORES THE TRANSCRIPTION ACTIVATION FUNCTION TO MUTANT P53

The p53 tumor suppressor is a transcription factor frequently mutated in human malignancies. Tumor-derived p53 missense mutants are defectiv e in sequence-specific DNA binding and fail to activate p53 target gen es. mAb PAb421 was shown previously to restore DNA binding to selected p53 mutants in vitro. Here we shown that mAb PAb421 when microinjecte d into human SW480 colorectal carcinoma cells restores the transcripti on activation function to the resident mutant p53 (arg to his 273, pro to ser 309). Codon 273 is the second most frequent p53 missense mutan t found in human tumors. Our results lend support to the concept of re storing wild-type function to mutant p53 as a strategy for cancer ther apy.