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p53-dependent Induction of WAF1 by a Low-pH Culture Condition in Human Glioblastoma Cells¹

Department of Otorhinolaryngology, Fukui Medical School, Matsuoka Fukui 910-11, Japan [T. O., H. S.]; Department of Biology, Nara Medical University, Kashihara, Nara 634, Japan [X. W., A. T., K. O., T. O.]; and Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota 55455 [C. W. S.]

The effects of an acidic condition (pH 6.5) on WAF1 gene expression and p53 accumulation was investigated in human glioblastoma cells with different p53 statuses. WAF1 and p53 accumulation after treatment in acidic conditions was observed in A-172 cells carrying the wild-type p53 gene but not in T98G cells carrying the mutant p53 gene. Northern blot analysis showed that WAF1 gene activation by acidic conditions only occurred in A-172 cells. Consistent with this, activation of the binding of p53 to its specific DNA sequence by acidic stress was detected by gel mobility shift assay using p53 consensus sequence as a probe. Moreover, the increased WAF1 protein and mRNA levels that were due to acidic treatment returned to normal levels upon the return of the cells to neutral conditions, 6 h after the cells had been cultured in acidic conditions for 6 or 12 h. These findings suggest that WAF1 gene activation is inducible by acidic conditions in human glioblastoma cells, which is probably due to activation of the p53-dependent signal transduction pathway.

¹ This work was supported in part by a grant from the Ministry of Education, Science and Culture of Japan.

² To whom requests for reprints should be addressed, at Department of Biology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan. Phone: 81-7442-2-3051 ext. 2264; Fax: 81-7442-5-3345. E-mail: tohnishi@nmu-gw.cc.naramed-u.ac.jp.

Received 5/ 1/97. Accepted 7/24/97.

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