1. Induction of senescence-like state and suppression of telomerase activity through inhibition of HPV E6/E7 gene expression in cells immortalized by HPV16 DNA
- Author
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Chan Jae Lee, Hyun Tae Kang, Eun Seong Hwang, Eun Jung Suh, Jun Sub Im, Soo-Jong Um, and Jong Sup Park
- Subjects
Senescence ,Cyclin-Dependent Kinase Inhibitor p21 ,Gene Expression Regulation, Viral ,Telomerase ,Cell division ,Papillomavirus E7 Proteins ,Cell Cycle Proteins ,Retinoblastoma Protein ,Viral Proteins ,Cyclins ,Tumor Cells, Cultured ,Animals ,Humans ,Papillomaviridae ,Cellular Senescence ,Bovine papillomavirus ,Regulation of gene expression ,biology ,Cell growth ,Cell Biology ,Oncogene Proteins, Viral ,biology.organism_classification ,Molecular biology ,E2F Transcription Factors ,DNA-Binding Proteins ,Repressor Proteins ,Cell culture ,DNA, Viral ,Cattle ,Tumor Suppressor Protein p53 ,Biomarkers ,Cell Division ,HeLa Cells ,Transcription Factors - Abstract
The E6 and E7 oncoproteins of human papillomavirus (HPV) play a major role in the development of cervical carcinoma. In this study, a recombinant adenovirus that expresses the bovine papillomavirus (BPV) E2, which has been shown to inhibit HPV early gene expression, was delivered to two HPV-immortalized cell lines as well as CaSki, a cervical carcinoma cell line. We tested whether the carcinoma and the immortal cells were equally affected by the expression of BPV E2. In all cell lines, BPV E2-mediated inhibition of HPV E6/E7 expression caused a dramatic suppression of cell growth, being preceded by the activation of the p53–Rb growth-inhibitory pathway, and a decrease in hTERT mRNA expression and telomerase activity. This suggests that the HPV E6 and E7 proteins are required not only for induction of the proliferative phenotype and telomerase activity, but also for their maintenance. In both the carcinoma and the immortal lines, the number of cells with enlarged cytoplasm and senescence-associated β-galactosidase activity, which are markers for cellular senescence, was significantly increased. These results suggest that a senescence program exists in cells immortalized by HPV DNA as well as in cervical carcinoma cells.
- Published
- 2002