Inhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by mutant p53
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Ημερομηνία
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Cell Growth Differ
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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.
Περιγραφή
Λέξεις-κλειδιά
Brain Neoplasms/*drug therapy/pathology, Cell Cycle/drug effects/genetics, Cell Division/drug effects/genetics, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases/*antagonists & inhibitors, Cyclins/*pharmacology, Enzyme Inhibitors/*pharmacology, *Genes, p53, Glioblastoma/*drug therapy/pathology, Humans, Mutation, Transfection, Tumor Cells, Cultured
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/8547219
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής