p53-RI75H mutant gains new function in regulation of doxorubicin-induced apoptosis
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AbstractMutation of tumor suppressor p53 gene gains new function in regulation of DNA damage-induced apoptotic response in tumor cells, which may lead to a poor response in cancer chemotherapy and radiotherapy. Transfection of mutant p53 (R175H) to p53-null osteosarcoma Saos-2 cells suppressed apoptosis induced by doxorubicin (DOX), cisplatin and gamma radiation. Downregulation of caspase-3 but not -8 or -9 basal protein levels was also observed in Saos-2 cells transfected with p53-R175H. After 48 hr of DOX treatment, the rate of procasapse-3 activation into 17 kDa active form was about 3-fold higher in the control cells than that in the p53-R175H counterpart. Gene silencing of p53-R175H expression by p53 siRNA upregulate the procaspase-3 protein level and restored DOX-induced apoptosis in p53-R175H cells. Our results suggest that p53-R175H mutation may gain new function in decreasing DOX-induced apoptotic response through suppression of caspase-3 level and its activation. (C) 2005 Wilely-Liss, Inc.
All Author(s) ListTsang WP, Ho FYF, Fung KP, Kong SK, Kwok TT
Journal nameInternational Journal of Cancer
Year2005
Month4
Day10
Volume Number114
Issue Number3
PublisherWILEY-LISS
Pages331 - 336
ISSN0020-7136
eISSN1097-0215
LanguagesEnglish-United Kingdom
Keywordscaspase-3; doxorubicin; p53 mutation
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2021-26-02 at 00:42