Transformation of normal human cells in the absence of telomerase activation
Open accessAbstract
Our knowledge of the transformation process has emerged largely from studies of primary rodent cells and animal models. However, numerous attempts to transform human cells using oncogene combinations that are effective in rodents have proven unsuccessful. These findings strongly argue for the study of homologous experimental systems. Here we report that the combined expression of adenovirus E1A, Ha-RasV12, and MDM2 is sufficient to convert a normal human cell into a cancer cell. Notably, transformation did not require telomerase activation. Therefore, we provide evidence that activation of telomere maintenance strategies is not an obligate characteristic of tumorigenic human cells.
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E1A facilitates Ras-induced transformation.
“The adenoviral oncoprotein E1A is known for blocking Ras senescence (43), facilitating Ras-induced transformation (42).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [42]
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- Authors
- Seger, Y. R., Garcı́a-Cao, M., Piccinin, S., Cunsolo, C. L., Doglioni, C., Blasco, M. A., Hannon, G. J., & Maestro, R.
- Affiliations
- State University of New York (US)
- Centro di Riferimento Oncologico (IT)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Hannon, Gregory J.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 2
- Issue
- 5
- Pages
- 401-413
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2113884084
- Cited by
- 159
- References
- 20
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 3 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 6
- FWCI
- 12.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Funders
- National Cancer Institute (2P01-CA13106, P01CA013106)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cell transformation, telomerase, telomere maintenance, adenovirus E1A, MDM2, human cell lines, carcinogenesis, telomere length
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Cell Transformation, Viral, Cells, Cultured, Chromosome Aberrations, Enzyme Activation, Fibroblasts, Humans, Mice, Nude, Retroviridae, Telomere, Cell Transplantation, Telomerase, Mice
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