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Departments of Neuro-Oncology [(C. G-M., J. F., A. P. K., V. A. L., W. K. A. Y.], Thoracic Surgery [J. A. R.], Molecular Pathology [T. J. M.], and Pathology [K. D. S.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Wild-type p53 is involved in several aspects of cell cycle control and suppression of transformation, inducing either apoptosis or G1 block in cell cycle progression. Using a recombinant adenovirus containing the wild-type p53 cDNA, the biological effects of the newly expressed wild-type p53 protein were examined in six human glioma cell lines. Three cell lines (U-251 MG, U-373 MG, and A-172) expressed endogenous mutant p53, and the other three (U-87 MG, EFC-2, and D54 MG) expressed wild-type p53. The restoration of normal p53-encoded protein in the mutant cell lines induced apoptosis as assessed by morphological studies using nuclear staining, electron microscopy, and flow cytometric assays. In wild-type p53 cell lines, however, the overexpression of wild-type p53 did not result in apoptosis but inhibited cellular proliferation rather drastically and modified the neoplastic phenotype. Differential effects suggest two pathways for glioma oncogenesis and a possible therapeutic strategy.
1 This work was supported in part by NIH Grants RO1-CA-51148, RO1-CA-56041, and PO1-CA-55261, and a Grant from the Gilland Foundation. C. G-M. and J. F. were supported by Grants FIS 94/5372 and FIS 94/5583 from the Ministerio de Sanidad, Madrid, Spain. T. J. M. is a Pew Scholar in the Biomedical Sciences.
2 To whom requests for reprints should be addressed, at Department of Neuro-Oncology, Box 100, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Received 9/ 5/95. Accepted 12/29/95.
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