Adenovirus-mediated overexpression of the transcription factor E2F-1 induces apoptosis in human breast and ovarian carcinoma cell lines and does not require p53.
Apoptosis is a mode of cell death that is carefully regulated based on cellular and environmental signals. The ability to modulate the individual cellular machinery and thereby to promote apoptosis is an important strategy in cancer therapy. It has previously been shown that overexpression of the transcription factor E2F-1 can induce apoptosis in quiescent rat embryo fibroblasts. This effect has been reported to occur in a p53-dependent manner. To investigate whether overexpression of E2F-1 could also induce apoptosis in human cancer cells, a recombinant adenovirus vector containing the transgene E2F-1 under control of the cytomegalovirus promoter (Ad5CMVE2F) was used to induce high levels of the E2F-1 protein in human breast and ovarian carcinoma cell lines. Significant morphological changes occurred in four of the five cell lines within 48 h of transduction with the Ad5CMVE2F. These changes were consistent with apoptosis, which was confirmed further by DNA fragmentation assay and fluorescence-activated cell sorting analysis. On the basis of these assays, which show that apoptosis occurred in those cell lines with mutations in the p53 gene, we suggest that the induction of E2F-1-mediated apoptosis does not require wild-type p53 when E2F-1 is overexpressed using an adenovirus-based strategy.
Hunt
K K
KK
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Deng
J
J
Liu
T J
TJ
Wilson-Heiner
M
M
Swisher
S G
SG
Clayman
G
G
Hung
M C
MC
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D005434:Flow Cytometry; D016161:Genes, Retinoblastoma / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors