Multiple stages of malignant transformation of human endothelial cells modelled by co-expression of telomerase reverse transcriptase, SV40 T antigen and oncogenic N-ras Journal Article

  

Authors:	Mackenzie, K. L.; Franco, S.; Naiyer, A. J.; May, C.; Sadelain, M.; Rafii, S.; Moore, M. A. S.
Article Title:	Multiple stages of malignant transformation of human endothelial cells modelled by co-expression of telomerase reverse transcriptase, SV40 T antigen and oncogenic N-ras
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 coexpressing 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.
Keywords:	telomerase; oncogenes; endothelial cells; transformation; immortalization
Journal Title:	Oncogene
Volume:	21
Issue:	27
ISSN:	0950-9232
Publisher:	Nature Publishing Group
Date Published:	2002-06-20
Start Page:	4200
End Page:	4211
Language:	English
DOI:	10.1038/sj.onc.1205425
PROVIDER:	scopus
PUBMED:	12082607
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047700179&doi=10.1038%2fsj.onc.1205425&partnerID=40&md5=7b1b7c6d35f8f1862e4e085428295a01
Notes:	Article -- Export Date: 2 July 2018 -- Source: Scopus

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