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rdf:type |
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lifeskim:mentions |
umls-concept:C0012860,
umls-concept:C0035820,
umls-concept:C0086418,
umls-concept:C0334227,
umls-concept:C0345904,
umls-concept:C0450442,
umls-concept:C0871261,
umls-concept:C1099354,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
4
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pubmed:dateCreated |
2005-9-5
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pubmed:abstractText |
Fimbrins (also known as plastins) are actin-binding proteins of the cortical cytoskeleton present in all cells and conserved from yeast to mammals. We previously reported that the up-regulation of T-fimbrin, a fimbrin isoform, in association with G2 arrest following DNA damage and that a lack of T-fimbrin expression shortens the radiation-induced G2 arrest in Chinese hamster ovarian cells. In this study, we further investigated the role of T-fimbrin in DNA-damage response using a panel of human liver cancer cell lines and small interfering RNA technology. T-fimbrin was differentially expressed in human liver cancer cell lines. Colony formation assays revealed that cell lines lacking T-fimbrin expression were highly sensitive to DNA damage compared to cell lines that express T-fimbrin. Using siRNA designed to target T-fimbrin, we demonstrated that silencing endogenous T-fimbrin causes a marked increase in the cellular sensitivity to VP-16 and UV irradiation. Moreover, T-fimbrin deletion abrogated UV-mediated cell cycle checkpoint, and consequently led to increased apoptotic cell death in resistant cells. These findings suggest that the status of T-fimbrin expression may be a useful molecular marker for predicting the responsiveness of cancer cells to treatment with chemotherapeutic drugs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/decitabine,
http://linkedlifedata.com/resource/pubmed/chemical/plastin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1019-6439
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
933-40
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pubmed:dateRevised |
2008-9-3
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pubmed:meshHeading |
pubmed-meshheading:16142308-Actins,
pubmed-meshheading:16142308-Antineoplastic Agents,
pubmed-meshheading:16142308-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:16142308-Apoptosis,
pubmed-meshheading:16142308-Azacitidine,
pubmed-meshheading:16142308-Carcinogens,
pubmed-meshheading:16142308-Cell Cycle,
pubmed-meshheading:16142308-Cell Line, Tumor,
pubmed-meshheading:16142308-Cell Separation,
pubmed-meshheading:16142308-Cytoskeleton,
pubmed-meshheading:16142308-DNA Damage,
pubmed-meshheading:16142308-DNA Methylation,
pubmed-meshheading:16142308-Etoposide,
pubmed-meshheading:16142308-Flow Cytometry,
pubmed-meshheading:16142308-G2 Phase,
pubmed-meshheading:16142308-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16142308-Gene Silencing,
pubmed-meshheading:16142308-Humans,
pubmed-meshheading:16142308-Immunoblotting,
pubmed-meshheading:16142308-Liver Neoplasms,
pubmed-meshheading:16142308-Membrane Glycoproteins,
pubmed-meshheading:16142308-Microfilament Proteins,
pubmed-meshheading:16142308-Microscopy, Fluorescence,
pubmed-meshheading:16142308-Protein Isoforms,
pubmed-meshheading:16142308-RNA, Small Interfering,
pubmed-meshheading:16142308-RNA Interference,
pubmed-meshheading:16142308-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16142308-Time Factors,
pubmed-meshheading:16142308-Transfection,
pubmed-meshheading:16142308-Ultraviolet Rays
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pubmed:year |
2005
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pubmed:articleTitle |
The role of T-fimbrin in the response to DNA damage: silencing of T-fimbrin by small interfering RNA sensitizes human liver cancer cells to DNA-damaging agents.
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pubmed:affiliation |
The First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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