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Department of Head and Neck Surgery [T-J. L., D. L. T., H. G., G. L. C.], Section of Thoracic Molecular Oncology, and Department of Thoracic and Cardiovascular Surgery [W-W. Z., J. A. R.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Mutations of the p53 gene constitute one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN). In this study, we introduced wild-type p53 into two separate SCCHN cell lines via a recombinant adenoviral vector, Ad5CMV-p53. Northern blotting showed that following infection by the wild-type p53 adenovirus (Ad5CMV-p53), cells produced up to 10-fold higher levels of exogenous p53 mRNA than cells treated with vector only (without p53). Western blotting showed that the increased levels of p53 protein produced in the Ad5CMV-p53-infected cells were a reflection of p53 mRNA expression. In vitro growth assays revealed growth arrest following Ad5CMV-p53 infection as well as cell morphological changes consistent with apoptosis. In vivo studies in nude mice with established s.c. squamous carcinoma nodules showed that tumor volumes were significantly reduced in mice that received peritumoral infiltration of Ad5CMV-p53. These data suggest that Ad5CMV-p53 may be further developed as a potential novel therapeutic agent for SCCHN since introduction of wild-type p53 into SCCHN cell lines attenuates their replication and tumor growth.
1 This work was supported in part by: American Cancer Society Career Development Award 93-9 (to G. L. C.); M. D. Anderson Cancer Center Core Grant NIH-NCI-CA-16672; Grant R01 CA-45187 from the National Cancer Institute and Training Grant CA09611 (both to J. A. R.); by gifts to the Division of Surgery from Tenneco and Exxon for the Core Lab Facility; the University of Texas M. D. Anderson Cancer Center Core Grant CA16672; and by a generous gift from the Mathers Foundation.
2 To whom requests for reprints should be addressed, at M. D. Anderson Cancer Center, Department of Head and Neck Surgery, Box 69, 1515 Holcombe Boulevard, Houston, TX 77030.
Received 4/18/94. Accepted 6/ 2/94.
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