Cell Growth & Differentiation, Vol 6, Issue 8 909-913, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Inhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by mutant p53

JM Jung, H Li, T Kobayashi, AP Kyritsis, LA Langford, JM Bruner, VA Levin and W Zhang
Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell cycle. The WAF1/Cip1 protein binds to the cyclin-dependent kinase complexes and inhibits the kinase activity that is required for cell cycle progression. We investigated the expression of WAF1/Cip1 protein in 14 glioblastoma cell lines and found that WAF1/Cip1 expression was detectable in many of the cell lines, even when mutant p53 was present. We also showed that WAF1/Cip1 protein level was very low in LN-Z308 cells that do not express endogenous p53. Transfection of the wild-type p53 into this cell line activated WAF1/Cip1 expression and inhibited cell growth. In contrast, transfection of the p53 mutant 248Trp failed to activate WAF1/Cip1 expression. Transfection of WAF1/Cip1 alone also inhibited LN-Z308 cell proliferation. However, cotransfection of the p53 mutant 248Trp with WAF1/Cip1 attenuated the growth-suppression effect of WAF1/Cip1. Our analysis with Western blot showed that the levels of cyclin E increased in cells transfected with p53 mutants. We conclude that p53 mutants may counter the negative regulators, such as WAF1/Cip1, by the elevation of positive cell cycle regulators, and the presence of WAF1/Cip1 in tumor cells is not sufficient for growth inhibition.

This article has been cited by other articles:

				Y. Hirose, M. S. Berger, and R. O. Pieper p53 Effects Both the Duration of G2/M Arrest and the Fate of Temozolomide-treated Human Glioblastoma Cells Cancer Res., March 1, 2001; 61(5): 1957 - 1963. [Abstract] [Full Text]