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Comparison of human mammary epithelial cells immortalized by simian virus 40 T-Antigen or by the telomerase catalytic subunit
Abstract
We directly compared two methods of immortalizing human mammary epithelial cells (HMECs). Cells were transfected with an expression plasmid either for hTERT, the catalytic subunit of telomerase, or for the simian virus 40 (SV40) early region genes. Under standard culture conditions, HMECs were not immortalized by hTERT unless they had spontaneously ceased expression of the p16(INK4a) tumor suppressor gene. Untransfected HMECs had low levels of telomerase expression, and immortalization by both methods was associated with an increase in telomerase activity and prevention of telomere shortening. SV40-induced immortalization was accompanied by aberrant differentiation, loss of DNA damage response, karyotypic instability and, in some cases, tumorigenicity. hTERT-immortalized cells had fewer karyotypic changes, but had intact DNA damage responses, and features of normal differentiation. Although SV40-immortalized cells are useful for studies of carcinogenesis, hTERT-immortalized cells retain more properties of normal cells.
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“Additionally, in many studies, hTERT-immortalized cells have been transformed into various differentiated cell types, exhibiting tissue-specific characteristics and unique proteins and forming structures similar to those inside the body [125].”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [125]
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“…R Reddel; E-mail: rreddel@cmri.usyd.edu.au Received 28 June 2001; revised 29 September 2001; accepted 1 October 2001 Immortalization of cells transformed with DNA tumor virus oncogenes is also associated with activation of a telomere maintenance mechanism, usually telomerase (Counter et al., 1992).”
BackgroundInfluentialControl of telomere length by the human telomeric protein TRF1
van Steensel, B., & de Lange, T. (1997) · Nature · doi:10.1038/385740a0 · Cited by 1,219
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Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions
Ramirez, R. D., Morales, C. P., Herbert, B.-S., Rohde, J. M., Passons, C., Shay, J. W., & Wright, W. E. (2001) · Genes & Development · doi:10.1101/gad.859201 · Cited by 444 · cited 4×
“, 1994), and the induction of telomerase activity (Elenbaas et al., 2001; Farwell et al., 2000; Kiyono et al., 1998; Ramirez et al., 2001; Stampfer et al., 2001).”
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“Post-selection HMECs have low or undetectable levels of p16 expression, associated with hypermethylation of CpG islands in the p16 gene (Brenner et al., 1998; Foster et al., 1998; Huschtscha et al., 1998).”
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CRISPR screens identify gene targets at breast cancer risk loci
Tuano, N. K., Beesley, J., Manning, M., Shi, W., Perlaza-Jimenez, L., Malaver-Ortega, L. F., Paynter, J. M., Black, D., Civitarese, A., McCue, K., et al. (2023) · Genome Biology · doi:10.1186/s13059-023-02898-w · Cited by 30
Self-citationReview of hTERT-Immortalized Cells: How to Assess Immortality and Confirm Identity
Shitova, M., Alpeeva, E., & Vorotelyak, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313054 · Cited by 22
Metadata
- Authors
- Toouli, C. D., Huschtscha, L. I., Neumann, A. A., Noble, J. R., Colgin, L. M., Hukku, B., & Reddel, R. R.
- Venue
- Oncogene
- Published
- 2002-01-03
- Volume
- 21
- Issue
- 1
- Pages
- 128-139
- ISSN
- 0950-9232
- 1476-5594
- Cited by
- 125
- References
- 9
- Language
- en
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