Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts
Open accessAbstract
In contrast to rodent cells, normal human fibroblasts are generally resistant to neoplastic transformation in vitro. Here, we report the derivation and characterization of a spontaneously transformed cell line from normal human IMR90 fibroblasts transduced with E1A and Ras oncogenes. Unlike the parental, non-tumorigenic E1A/Ras-expressing IMR90 cells, these spontaneously transformed cells displayed aberrant growth potential in vitro and were capable of tumorigenesis in vivo. In contrast to the parental E1A/Ras-expressing cells, both the spontaneously transformed cells and cells derived from resultant tumors displayed specific t(7q;8q) and t(5q;17) structural chromosomal changes. Chromosome 8q contains c-Myc, which is capable of activating the telomerase catalytic subunit hTERT. Notably, upregulation of c-Myc, hTERT and telomerase activity were detected only in the tumorigenic cells. Transduction of Myc siRNA into the tumorigenic cells led to a concomitant downregulation of hTERT. Furthermore, transduction of Myc or hTERT into the non-tumorigenic E1A/Ras-expressing IMR90 cells was able to confer tumorigenesis on these cells. These studies suggest that the t(7;8) translocation may result in Myc overexpression and its subsequent activation of hTERT, which may contribute to the tumorigenicity of the IMR90 cells. Furthermore, this report describes additional successful neoplastic transformation of human IMR90 fibroblasts by defined genetic elements. The spontaneously transformed cells we have derived provide a valuable model system for the study of neoplastic transformation.
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Senescent cells produce increased amounts of secreted proteins, including extracellular proteases, matrix components, growth factors, cytokines, and chemokines.
“it is striking to note that senescent cells produce increased amounts of secreted proteins, including extracellular proteases and matrix components, growth factors, cytokines, and chemokines (Mason et al., 2006; Shelton et al., 1999”
From Chemokine signaling via the CXCR2 receptor reinforces senescence (2008) · cites this paper as Mason et al., 2006
The Introduction discusses senescence as a barrier to cell proliferation, not changes in protein secretion. Searches for secreted proteins, proteases, matrix components, growth factors, cytokines, and chemokines found no passage in our copy addressing the claimed increase. (LLM, conf=0.76)
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“One important safeguard against neoplastic transformation is replicative senescence [3].”
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Chemokine signaling via the CXCR2 receptor reinforces senescence
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- Authors
- Mason, D. X., Keppler, D., Zhang, J., Jackson, T. J., Seger, Y. R., Matsui, S., Abreo, F., Cowell, J. K., Hannon, G. J., Lowe, S. W., & Lin, A. W.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- Louisiana State University in Shreveport (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Mason, Douglas X.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-08-25
- Volume
- 27
- Issue
- 2
- Pages
- 350-359
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- PMC
- PMC4590994
- OpenAlex
- W2098660451
- Cited by
- 18
- References
- 3
- Citations by year
- 2025: 1 · 2023: 3 · 2015: 2 · 2014: 2 · 2012: 1
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- American Cancer Society (CA16056)
- Roswell Park Cancer Institute (CA16056)
- National Cancer Institute (CA 16056., R21 CA9124785, P01CA013106, P30CA008748, P30CA016056)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Keywords
- IMR-90 fibroblasts, E1A oncogene, oncogenic Ras, c-Myc, hTERT, telomerase, chromosome 8q, carcinogenesis, human fibroblasts
- MeSH terms
- Cell Transformation, Neoplastic, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, Humans, Genes, ras, Transduction, Genetic, Translocation, Genetic, Tumor Cells, Cultured, Genes, myc, Adenovirus E1A Proteins, Cell Culture Techniques, Telomerase, Genetic Predisposition to Disease
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