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Molecular determinants of cell death induction following adenovirus‐mediated gene transfer of wild‐type p53 in prostate cancer cells
Author(s) -
Schumacher Guido,
Bruckheimer Elizabeth M.,
Beham Alexander W.,
Honda Tsuyoshi,
Brisbay Shawn,
Roth Jack A.,
Logothetis Christopher,
McDonnell Timothy J.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1026>3.0.co;2-n
Subject(s) - lncap , prostate cancer , cancer research , apoptosis , programmed cell death , transfection , biology , prostate , viability assay , cancer cell , cancer , cell culture , genetics
Adenoviral vectors expressing wild‐type p53 (Ad‐p53) induce apoptosis in different types of cancer cells. The therapeutic utility of Ad‐p53 is now being evaluated in prostate‐cancer patients. Bcl‐2 is frequently expressed by prostate‐cancer cells and has previously been shown to inhibit p53‐mediated cell death following genotoxic stress. We studied the impact of bcl‐2 on Ad‐p53–induced cell death in human prostate‐cancer cells. Human prostate‐cancer cell lines LNCaP (p53 wt) and PC3 (p53 mut) were stably transfected with bcl‐2. After p53 transduction, cell viability, apoptosis induction and modulation of specific apoptosis‐regulatory proteins were assessed. LNCaP vector control and bcl‐2–expressing cells underwent similar decreases in viability associated with apoptosis induction following Ad‐p53 infection. Increased bcl‐2 expression provided significant protection to PC3 cells transduced with Ad‐p53. These findings are correlated with modulations in bax, bcl‐2, bcl‐x L and p21 protein levels. These data suggest that Ad‐p53 may be useful in the treatment of some prostate cancers. © 2001 Wiley‐Liss, Inc.