ArticleOncogene2002
Multiple stages of malignant transformation of human endothelial cells modelled by co-expression of telomerase reverse transcriptase, SV40 T antigen and oncogenic N-ras.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Establishment and characterization of immortalized porcine neonatal hepatocytes without the use of viral components.In vitro cellular & developmental biology. Animal · 2020Article
- A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration.Cell & bioscience · 2019Review
- Establishment, characterization, and toxicological application of a spontaneous immortalized cell line from the striped field mouse, Apodemus agrarius.In vitro cellular & developmental biology. Animal · 2018Article
- Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder.Journal of translational medicine · 2017Review
- New prospects for targeting telomerase beyond the telomere.Nature reviews. Cancer · 2016Review
- The renewed battle against RAS-mutant cancers.Cellular and molecular life sciences : CMLS · 2016Review
- Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study.EBioMedicine · 2016Article
- γ-Actin plays a key role in endothelial cell motility and neovessel maintenance.Vascular cell · 2015Article
- Telomeres are elongated in rats exposed to moderate altitude.Journal of physiological anthropology · 2014Article
- Modeling human endothelial cell transformation in vascular neoplasias.Disease models & mechanisms · 2013Review
- β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma.British journal of cancer · 2013Article
- Up-regulation of survivin during immortalization of human myofibroblasts is linked to repression of tumor suppressor p16(INK4a) protein and confers resistance to oxidative stress.The Journal of biological chemistry · 2013Article
- Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Concentration- and schedule-dependent effects of chemotherapy on the angiogenic potential and drug sensitivity of vascular endothelial cells.Angiogenesis · 2013Article
- HDAC inhibitors induce tumor-cell-selective pro-apoptotic transcriptional responses.Cell death & disease · 2013Article
- Endothelial cell dysfunction and cytoskeletal changes associated with repression of p16(INK4a) during immortalization.Oncogene · 2012Article
- Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment.Oncotarget · 2011Article
- Benign mesenchymal stromal cells in human sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Article
- Malignant transformation in a defined genetic background: proteome changes displayed by 2D-PAGE.Molecular cancer · 2010Article
- Upregulation of survivin during immortalization of nontransformed human fibroblasts transduced with telomerase reverse transcriptase.Oncogene · 2009Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
We have modelled multiple stages of malignant transformation of human endothelial cells (ECs) by overexpressing the catalytic subunit of human telomerase (hTERT), together with SV40 T antigen (SV40T) and oncogenic N-ras. Transfection with hTERT alone, led to the immortalization of two out of three cultures of bone marrow-derived ECs (BMECs). One hTERT transduced BMEC culture underwent a long proliferative lag before resuming proliferation. BMECs transfected with hTERT alone were functionally and phenotypically normal. BMECs transfected with SV40T (BMSVTs) had an extended lifespan, but eventually succumbed to crisis. BMSVTs exhibited a partially transformed phenotype, demonstrating growth factor independence, altered antigen expression and forming tiny, infrequent colonies in vitro. Transduction of BMSVTs with hTERT resulted in immortalization of 4 out of 4 cultures. BMSVTs immortalized with hTERT formed large colonies in vitro and small transient tumours in vivo. BMECs co-expressing SV40T, hTERT and N-ras exhibited an overtly transformed phenotype; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo. These investigations demonstrate transformation of human ECs to an overtly malignant phenotype. This model will be useful for understanding mechanisms underlying vascular and angiogenic neoplasias, as well as for testing drugs designed to curtail aberrant EC growth.
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