| Senescence and immortality in hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 19070423 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment. |
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Authors:
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Mehmet Ozturk; Ayca Arslan-Ergul; Sevgi Bagislar; Serif Senturk; Haluk Yuzugullu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2008-12-12 |
Journal Detail:
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Title: Cancer letters Volume: 286 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-09 Completed Date: 2009-11-16 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 103-13 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey. ozturkm@ujf-grenoble.fr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Carcinoma, Hepatocellular
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pathology* Cell Aging* Cell Transformation, Neoplastic / genetics* Cyclin-Dependent Kinases / antagonists & inhibitors Enzyme Activation Hepatocytes / pathology Humans Liver Neoplasms / pathology* Protein Kinase Inhibitors Telomerase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Protein Kinase Inhibitors; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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