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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Bibliographic Details
Published in:Oncogene Vol. 25; no. 7; pp. 990 - 997
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 16.02.2006
Nature Publishing
Nature Publishing Group
Nature Publishing Group [1987-....]
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1209135