Clinical Cancer Research, Vol 3, Issue 2 185-191, Copyright © 1997 by American Association for Cancer Research

ARTICLES

Head and neck squamous cell growth suppression using adenovirus-p53-FLAG: a potential marker for gene therapy trials

SM Overholt, TJ Liu, DL Taylor, M Wang, AK El-Naggar, E Shillitoe, K Adler-Storthz, LS John, WW Zhang, JA Roth and GL Clayman
Departments of Head and Neck Surgery, Section of Thoracic Molecular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

The recombinant wild-type p53 adenovirus has been proven effective against the growth of human head and neck squamous cell cancer (SCCHN) cell lines iir vitro and in a nude mouse model. The addition of a FLAG peptide sequence was used in this study, along with the p53 adenovirus vector as a marker of the site of the gene therapy activity. It provides clear evidence of the exogenous gene product within the transduced carcinoma cells. No alterations in transcription or translation of the p53 gene product were noted with the addition of the FLAG sequence to the original p53 adenovirus vector. Immunohistochemical analysis displayed simultaneous expression of the p53 and FLAG proteins in the infected cells. The p53 protein remained localized to the nucleus, whereas the FLAG protein was additionally noted in the cytoplasm. In vitro growth suppression assays and in vivo microscopic residual tumor model experiments in nude mice showed a similar tumoricidal effect with the p53-FLAG adenovirus vector to that with the previously studied p53 adenovirus vector without the addition of the FLAG sequence. We conclude that the addition of the FLAG octapeptide sequence allows identification of those cells that have been affected by the molecular therapy independent of the endogenous gene expression of the cells. This novel molecular tracer may prove useful in characterizing infection efficiency and in gene therapy trials.

This article has been cited by other articles:

				M. L. Figueiredo, Y. Kim, M. A.R. St. John, and D. T.W. Wong p12CDK2-AP1 Gene Therapy Strategy Inhibits Tumor Growth in an In vivo Mouse Model of Head and Neck Cancer Clin. Cancer Res., May 15, 2005; 11(10): 3939 - 3948. [Abstract] [Full Text] [PDF]