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Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements

Casillas, Mark A., Brotherton, Scott L., Andrews, Lucy G., Ruppert, J.Michael, Tollefsbol, Trygve O.·2003·Gene
DOI 10.1016/s0378-1119(03)00739-x
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Abstract

Elucidation of the mechanisms governing expression of the human telomerase reverse transcriptase (hTERT) is important for understanding cancer pathogenesis. Approximately 90% of tumors express hTERT, the major catalytic component of telomerase. Activation of telomerase is an early event, and high levels of this activity correlate with poor prognosis. Recent studies have shown that the transcription factors c-Myc and Mad1 activate and repress hTERT, respectively. It is not clear how these transcription factors compete for the same recognition sequence in the hTERT core promoter region. Studies have shown that the combined expression of SV40 large T antigen (T-Ag), hTERT, and H-Ras is able to transform human cells. In this study, we used a distinct human cell type, WI-38 fetal lung fibroblasts used extensively for senescence studies. We transduced cells with amphotropic retroviral constructs containing SV40 T antigen, hTERT, and activated H-ras. Transduced cells exhibited anchorage independence in soft agar and expressed increased levels of c-Myc and endogenous hTERT. These effects were observed by 25 population doublings (PDs) following the establishment of the neoplastic cell line. During the process of transformation, we observed a switch from Mad1/Max to c-Myc/Max binding to oligonucleotide sequences containing the hTERT promoter distal and proximal E-boxes. c-Myc can bind specifically to the hTERT promoter in vitro, indicating that c-Myc expression in tumors may account fo…

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Research works printed but not linked: 23

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Metadata

Authors
Casillas, M. A., Brotherton, S. L., Andrews, L. G., Ruppert, J. M., & Tollefsbol, T. O.
Venue
Gene
Publisher
Elsevier BV
Published
2003-10
Volume
316
Pages
57-65
ISSN
0378-1119
DOI
10.1016/s0378-1119(03)00739-x
Cited by
51
References
5
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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CoChat. (2026). Citation check: Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements. https://app.cochat.ai/papers/10.1016/s0378-1119(03)00739-x
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Casillas, M. A., Brotherton, S. L., Andrews, L. G., Ruppert, J. M., & Tollefsbol, T. O. (2003). Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements. Gene. https://doi.org/10.1016/s0378-1119(03)00739-x