Molecular determinants of cell death induction following adenovirus-mediated gene transfer of wild-type P53 in prostate cancer cells

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...

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Bibliographic Details
Published in:International journal of cancer 2001-01, Vol.91 (2), p.159-166
Main Authors: SCHUMACHER, Guido, BRUCKHEIMER, Elizabeth M, BEHAM, Alexander W, HONDA, Tsuyoshi, BRISBAY, Shawn, ROTH, Jack A, LOGOTHETIS, Christopher, MCDONNELL, Timothy J
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
adenovirus
Apoptosis
Biological and medical sciences
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - physiology
Genes, p53
Genetic Therapy
Genital system. Mammary gland
Humans
Male
Medical sciences
prostate caracinoma
Prostatic Neoplasms - pathology
Prostatic Neoplasms - therapy
Proto-Oncogene Proteins c-bcl-2 - analysis
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Tumor Cells, Cultured
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Summary: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.
ISSN:0020-7136
1097-0215
DOI:10.1002/1097-0215(200002)9999:9999<::AID-IJC1026>3.3.CO;2-E