TRF2 inhibition promotes anchorage-independent growth of telomerase-positive human fibroblasts

Although telomere instability is observed in human tumors and is associated with the development of cancers in mice, it has yet to be established that it can contribute to the malignant transformation of human cells. We show here that in checkpoint-compromised telomerase-positive human fibroblasts a...

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Vydáno v:	Oncogene Ročník 25; číslo 7; s. 990 - 997
Hlavní autoři:	Brunori, M, Mathieu, N, Ricoul, M, Bauwens, S, Koering, C E, Roborel de Climens, A, Belleville, A, Wang, Q, Puisieux, I, Décimo, D, Puisieux, A, Sabatier, L, Gilson, E
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 16.02.2006 Nature Publishing Nature Publishing Group Nature Publishing Group [1987-....]
Témata:	Alleles Animals Apoptosis Biological and medical sciences Cancer Cell Biology Cell Line, Transformed Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cells (Biology) Chromosomes Computer Science DNA damage Female Fibroblasts Fibroblasts - enzymology Fibroblasts - pathology Fundamental and applied biological sciences. Psychology Growth Human Genetics Humans Internal Medicine Life Sciences Medicine Medicine & Public Health Mice Mice, Nude Molecular and cellular biology Mutation Oncology original-article Simian virus 40 - genetics Telomerase Telomerase - metabolism Telomere-binding protein Telomeres Telomeric Repeat Binding Protein 2 - antagonists & inhibitors Telomeric Repeat Binding Protein 2 - genetics Telomeric Repeat Binding Protein 2 - metabolism Transfection TRF2 protein Tumorigenesis Tumors Yeast France malignant transformation TRF2 telomere Human Enzyme Growth Malignant transformation Chromosome Inhibition Carcinogenesis Fibroblast Telomerase Telomere TELOMERE CANCER GENOMIQUE MALIGNANT TRANSFORMATION
ISSN:	0950-9232, 1476-5594
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Popis
Shrnutí:	Although telomere instability is observed in human tumors and is associated with the development of cancers in mice, it has yet to be established that it can contribute to the malignant transformation of human cells. We show here that in checkpoint-compromised telomerase-positive human fibroblasts an episode of TRF2 inhibition promotes heritable changes that increase the ability to grow in soft agar, but not tumor growth in nude mice. This transforming activity is associated to a burst of telomere instability but is independent of an altered control of telomere length. Moreover, it cannot be recapitulated by an increase in chromosome breaks induced by an exposure to γ -radiations. Since it can be revealed in the context of telomerase-proficient human cells, telomere dysfunction might contribute to cancer progression even at late stages of the oncogenesis process, after the telomerase reactivation step.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0950-9232 1476-5594
DOI:	10.1038/sj.onc.1209135