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

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dc.contributor.authorJung, J. M.en
dc.contributor.authorLi, H.en
dc.contributor.authorKobayashi, T.en
dc.contributor.authorKyritsis, A. P.en
dc.contributor.authorLangford, L. A.en
dc.contributor.authorBruner, J. M.en
dc.contributor.authorLevin, V. A.en
dc.contributor.authorZhang, W.en
dc.date.accessioned2015-11-24T19:09:50Z
dc.date.available2015-11-24T19:09:50Z
dc.identifier.issn1044-9523-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/20755
dc.rightsDefault Licence-
dc.subjectBrain Neoplasms/*drug therapy/pathologyen
dc.subjectCell Cycle/drug effects/geneticsen
dc.subjectCell Division/drug effects/geneticsen
dc.subjectCyclin-Dependent Kinase Inhibitor p21en
dc.subjectCyclin-Dependent Kinases/*antagonists & inhibitorsen
dc.subjectCyclins/*pharmacologyen
dc.subjectEnzyme Inhibitors/*pharmacologyen
dc.subject*Genes, p53en
dc.subjectGlioblastoma/*drug therapy/pathologyen
dc.subjectHumansen
dc.subjectMutationen
dc.subjectTransfectionen
dc.subjectTumor Cells, Cultureden
dc.titleInhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by mutant p53en
heal.abstractThe 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.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/8547219-
heal.journalNameCell Growth Differen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate1995-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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