Linked Life Data

12082607

Source:http://linkedlifedata.com/resource/pubmed/id/12082607

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2002-6-25
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4200-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12082607-Adult, pubmed-meshheading:12082607-Animals, pubmed-meshheading:12082607-Antigens, Polyomavirus Transforming, pubmed-meshheading:12082607-Cell Aging, pubmed-meshheading:12082607-Cell Transformation, Neoplastic, pubmed-meshheading:12082607-Cell Transformation, Viral, pubmed-meshheading:12082607-Cells, Cultured, pubmed-meshheading:12082607-DNA-Binding Proteins, pubmed-meshheading:12082607-Endothelium, Vascular, pubmed-meshheading:12082607-Flow Cytometry, pubmed-meshheading:12082607-Genes, ras, pubmed-meshheading:12082607-Humans, pubmed-meshheading:12082607-Lung Neoplasms, pubmed-meshheading:12082607-Mice, pubmed-meshheading:12082607-Mice, Inbred NOD, pubmed-meshheading:12082607-Mice, Nude, pubmed-meshheading:12082607-Mice, SCID, pubmed-meshheading:12082607-Neoplasm Transplantation, pubmed-meshheading:12082607-Proto-Oncogene Proteins p21(ras), pubmed-meshheading:12082607-Recombinant Fusion Proteins, pubmed-meshheading:12082607-Telomerase, pubmed-meshheading:12082607-Telomere, pubmed-meshheading:12082607-Transfection, pubmed-meshheading:12082607-Transplantation, Heterologous, pubmed-meshheading:12082607-Tumor Stem Cell Assay
pubmed:year
2002
pubmed:articleTitle
Multiple stages of malignant transformation of human endothelial cells modelled by co-expression of telomerase reverse transcriptase, SV40 T antigen and oncogenic N-ras.
pubmed:affiliation
James Ewing Laboratory of Developmental Haematopoiesis and Department of Human Genetics, Sloan-Kettering Cancer Institute, New York, NY, USA. k.mackenzie@unsw.edu.au
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't