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PMID: 16461895 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 7 ·2006-02-14 ·Pages 2178-83

Ozturk N, Erdal E, Mumcuoglu M, Akcali KC, Yalcin O, Senturk S, Arslan-Ergul A, Gur B, Yulug I, Cetin-Atalay R, Yakicier C, Yagci T, Tez M, Ozturk M

Abstract

Tumor cells have the capacity to proliferate indefinitely that is qualified as replicative immortality. This ability contrasts with the intrinsic control of the number of cell divisions in human somatic tissues by a mechanism called replicative senescence. Replicative immortality is acquired by inactivation of p53 and p16INK4a genes and reactivation of hTERT gene expression. It is unknown whether the cancer cell replicative immortality is reversible. Here, we show the spontaneous induction of replicative senescence in p53-and p16INK4a-deficient hepatocellular carcinoma cells. This phenomenon is characterized with hTERT repression, telomere shortening, senescence arrest, and tumor suppression. SIP1 gene (ZFHX1B) is partly responsible for replicative senescence, because short hairpin RNA-mediated SIP1 inactivation released hTERT repression and rescued clonal hepatocellular carcinoma cells from senescence arrest.

MeSH Terms
Animals Carcinoma, Hepatocellular/genetics,pathology Cell Line, Tumor Cellular Senescence/genetics Cyclin-Dependent Kinase Inhibitor p16/deficiency,genetics DNA-Binding Proteins/genetics Down-Regulation Genes, Neoplasm Homeodomain Proteins/genetics Humans Liver Neoplasms/genetics,pathology Mice Repressor Proteins/genetics Telomerase/genetics Tumor Suppressor Protein p53/deficiency,genetics Zinc Finger E-box Binding Homeobox 2
Chemicals
Cyclin-Dependent Kinase Inhibitor p16 DNA-Binding Proteins Homeodomain Proteins Repressor Proteins Tumor Suppressor Protein p53 ZEB2 protein, human Zinc Finger E-box Binding Homeobox 2 Telomerase
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Ozturk Nuri
Department of Molecular Biology and Genetics, Bilkent University, Bilkent, Ankara 06800, Turkey. ozturk@fen.bilkent.edu.tr
Erdal Esra
Mumcuoglu Mine
Akcali Kamil C
Yalcin Ozden
Senturk Serif
Arslan-Ergul Ayca
Gur Bala
Yulug Isik
Cetin-Atalay Rengul
Yakicier Cengiz
Yagci Tamer
Tez Mesut
Ozturk Mehmet
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0510877103
Email
ozturk@fen.bilkent.edu.tr
Published
2006-02-14
Epub
2006-00-06
Pages
2178-83
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1413736
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0510877103 PMC Full Text View journal details
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