Endogenous p53 gene status predicts the response of human squamous cell carcinomas to wild-type p53

Prior reports suggest that p53 protein status may influence the response to gene transduction with wild-type (wt) p53. Adenoviral vectors containing t he p53 gene were administered to normal keratinocytes, to squamous cell car cinoma (SCC) lines with varied p53 protein status (absent, mutant, wt, or d egraded by papillomavirus), as well as to tumors formed in severe combined immunodeficient mice. The percentage of cells undergoing apoptosis, G(1) gr owth arrest, WAFl/p21 induction, and in vivo tumor progression were studied after wt p53 gene transduction. Apoptosis developed first in normal kerati nocytes, next in SCCs lacking p53 protein, and last in SCCs with mutant or degraded p53 protein. All of the cell lines studied demonstrated an increas e in WAFl/p21 protein, but only those lacking p53 protein showed G(1) arres t. Tumors lacking p53 protein were more susceptible to p53 overexpression t han those containing mutant or degraded p53 protein. The endogenous p53 pro tein status of SCCs appears to influence the outcome of p53 gene transducti on.