GROWTH SUPPRESSION OF HUMAN HEAD AND NECK-CANCER CELLS BY THE INTRODUCTION OF A WILD-TYPE P53 GENE VIA A RECOMBINANT ADENOVIRUS

Mutations of the p53 gene constitute one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN). I n this study, we introduced wild-type p53 into two separate SCCHN cell lines via a recombinant adenoviral vector, Ad5CMV-p53. Northern blott ing showed that following infection by the wild-type p53 adenovirus (A d5CMV-p53), cells produced up to l0-fold higher levels of exogenous p5 3 mRNA than cells treated with vector only (without p53). Western blot ting showed that the increased levels of p53 protein produced in the A d5CMV-pS3-infected cells were a reflection of p53 mRNA expression. In vitro growth assays revealed growth arrest following Ad5CMV-p53 infect ion as well as cell morphological changes consistent with apoptosis. I n vivo studies in nude mice with established s.c. squamous carcinoma n odules showed that tumor volumes were significantly reduced in mice th at received peritumoral infiltration of Ad5CMV-p53. These data suggest that Ad5CMV-p53 may be further developed as a potential novel therape utic agent for SCCHN since introduction of wild-type p53 into SCCHN ce ll lines attenuates their replication and tumor growth.