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Rapid induction of senescence in human cervical carcinoma cells
Abstract
Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.
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“The integrated structure contains only two-thirds of the complete HPV-18 genome, including full-length copies of the E6 and E7 oncogenes necessary for telomerase activity (amplified to CN 12), but lacking a functional copy of E2, an inhibitor of E6 and E713 (Figure 2c).”
From The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line (2013) · cites this paper as [13]
In the citing paper
“However, three are associated with HPV-mediated oncogenesis (FGFR3, EP300, NOTCH1) and may be ancillary to the dominant role of HPV oncoproteins in HeLa and other HPV+ cervical carcinomas13.”
From The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line (2013) · cites this paper as [13]
In the citing paper
“the silencing or repression of these oncoproteins activates senescence and apoptosis of the HPV-transformed cells [17,18,19,122,123]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [123]
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Cited by
Senescence-associated β-galactosidase is lysosomal β-galactosidase.
Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444
Self-citationHallmarks of senescence in carcinogenesis and cancer therapy
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The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line
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Self-citationMolecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent
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Metadata
- Authors
- Goodwin, E. C., Yang, E., Lee, C.-J., Lee, H.-W., DiMaio, D., & Hwang, E.-S.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-09-26
- Volume
- 97
- Issue
- 20
- Pages
- 10978-10983
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 176
- References
- 3
- Language
- en
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