Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-8-2
pubmed:abstractText
Many human cancer cells lack telomerase activity but nevertheless maintain telomeres via a process termed "alternative lengthening of telomeres" (ALT). Despite being immortal and having a telomere maintenance mechanism, ALT+ human fibroblasts require telomerase reverse transcriptase (hTERT) for tumor formation in immunodeficient mice when tested by s.c. injection. Here we show that three ALT+ human SV40-immortalized fibroblast cell lines require only oncogenic RasV12G to be converted to a fully tumorigenic state. When cells were implanted beneath the kidney capsule of immunodeficient mice, they invaded the kidney and neighboring organs and metastasized to the lungs. Ras(V12G)-expressing ALT+ cells remained completely telomerase negative. Introduction of hTERT conferred strong telomerase activity but did not appreciably change the malignant properties of the cells. However, when cells were tested by s.c. injection, RasV12G-transduced ALT+ cells did not form tumors, and in this site, hTERT was required for tumorigenicity. These data show that when the s.c. injection method is used as an assay for tumorigenicity, hTERT may be artifactually scored as an oncogene; the subrenal capsule assay shows that ALT, as a telomere maintenance mechanism, is equivalent to hTERT in neoplastic transformation of human cells by oncogenes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6512-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Immortal ALT+ human cells do not require telomerase reverse transcriptase for malignant transformation.
pubmed:affiliation
Department of Physiology and Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78245, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural