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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-11-18
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pubmed:abstractText |
Focal adhesion kinase (FAK) is an important regulator of cellular signaling, migration, apoptosis, and cell cycle progression. We tested the hypothesis that FAK is a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells and examined the effect of inhibiting FAK expression on gemcitabine-induced cytotoxicity in vitro and in vivo. FAK expression was quantified by Western and Northern blots. Expression of FAK was suppressed using small interfering RNA (siRNA). Gemcitabine-induced cytotoxicity was quantified and apoptosis was characterized. Akt activity was determined by in vitro kinase assay. We assessed the therapeutic applicability of FAK siRNA in a nude mouse orthotopic xenograft model. While not affecting cellular proliferation or apoptosis in the absence of gemcitabine, FAK siRNA potentiated gemcitabine-induced cytotoxicity in vitro and in vivo. FAK siRNA treatment suppressed Akt activity, which may contribute to its chemosensitizing effect.
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/gemcitabine
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
311
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
786-92
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14623342-Adenocarcinoma,
pubmed-meshheading:14623342-Animals,
pubmed-meshheading:14623342-Apoptosis,
pubmed-meshheading:14623342-Blotting, Northern,
pubmed-meshheading:14623342-Blotting, Western,
pubmed-meshheading:14623342-Caspases,
pubmed-meshheading:14623342-Cell Line, Tumor,
pubmed-meshheading:14623342-Deoxycytidine,
pubmed-meshheading:14623342-Enzyme Inhibitors,
pubmed-meshheading:14623342-Focal Adhesion Kinase 1,
pubmed-meshheading:14623342-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:14623342-Humans,
pubmed-meshheading:14623342-Male,
pubmed-meshheading:14623342-Mice,
pubmed-meshheading:14623342-Mice, Nude,
pubmed-meshheading:14623342-Neoplasm Transplantation,
pubmed-meshheading:14623342-Pancreas,
pubmed-meshheading:14623342-Pancreatic Neoplasms,
pubmed-meshheading:14623342-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14623342-Protein-Tyrosine Kinases,
pubmed-meshheading:14623342-Proto-Oncogene Proteins,
pubmed-meshheading:14623342-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:14623342-RNA,
pubmed-meshheading:14623342-RNA, Small Interfering,
pubmed-meshheading:14623342-RNA Interference,
pubmed-meshheading:14623342-Transfection
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pubmed:year |
2003
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pubmed:articleTitle |
RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity.
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pubmed:affiliation |
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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