Inhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by mutant p53
Φόρτωση...
Ημερομηνία
Συγγραφείς
Jung, J. M.
Li, H.
Kobayashi, T.
Kyritsis, A. P.
Langford, L. A.
Bruner, J. M.
Levin, V. A.
Zhang, W.
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