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Transcriptional regulation during p21WAF1/CIP1-induced apoptosis in human ovarian cancer cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Sep 27; Vol. 277 (39), pp. 36329-37. Date of Electronic Publication: 2002 Jul 22. - Publication Year :
- 2002
-
Abstract
- In this study we used adenovirus vector-mediated transduction of either the p53 gene (rAd-p53) or the p21(WAF1/CIP1) gene (rAd-p21) to mimic both p53-dependent and -independent up-regulation of p21(WAF1/CIP1) within a human ovarian cancer cell line, 2774, and the derivative cell lines, 2774qw1 and 2774qw2. We observed that rAd-p53 can induce apoptosis in both 2774 and 2774qw1 cells but not in 2774qw2 cells. Surprisingly, overexpression of p21(WAF1/CIP1) also triggered apoptosis within these two cell lines. Quantitative reverse transcription-PCR analysis revealed that the differential expression of BAX, BCL2, and caspase 3 genes, specific in rAd-p53-induced apoptotic cells, was not altered in rAd-p21-induced apoptotic cells, suggesting p21(WAF1/CIP1)-induced apoptosis through a pathway distinguishable from p53-induced apoptosis. Expression analysis of 2774qw1 cells infected with rAd-p21 on 60,000 cDNA microarrays identified 159 genes in response to p21(WAF1/CIP1) expression in at least one time point with 2.5-fold change as a cutoff. Integration of the data with the parallel microarray experiments with rAd-p53 infection allowed us to extract 66 genes downstream of both p53 and p21(WAF1/CIP1) and 93 genes in response to p21(WAF1/CIP1) expression in a p53-independent pathway. The genes in the former set may play a dual role in both p53-dependent and p53-independent pathways, and the genes in the latter set gave a mechanistic molecular explanation for p53-independent p21(WAF1/CIP1)-induced apoptosis. Furthermore, promoter sequence analysis suggested that transcription factor E2F family is partially responsible for the differential expression of genes following p21(WAF1/CIP1). This study has profound significance toward understanding the role of p21(WAF1/CIP1) in p53-independent apoptosis.
- Subjects :
- Adenoviridae genetics
Caspase 3
Caspases metabolism
Cell Line
Cyclin-Dependent Kinase Inhibitor p21
Cyclins physiology
DNA, Complementary metabolism
Female
Genetic Vectors
Genome, Human
Humans
In Situ Nick-End Labeling
Oligonucleotide Array Sequence Analysis
Phenotype
Promoter Regions, Genetic
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Tumor Cells, Cultured
Tumor Suppressor Protein p53 metabolism
Up-Regulation
bcl-2-Associated X Protein
Apoptosis
Cyclins metabolism
Gene Expression Regulation, Neoplastic
Ovarian Neoplasms metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 39
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12138103
- Full Text :
- https://doi.org/10.1074/jbc.M204962200