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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2004-11-1
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pubmed:abstractText |
Malignant mesothelioma (MM) is strongly resistant to conventional chemotherapy by unclear mechanisms. We and others have previously reported that cytokine- and growth factor-mediated signal transduction is involved in the growth and progression of MM. Here, we identified a pathway that involves stem cell factor (SCF)/c-Kit/Slug in mediating multidrug resistance of MM cells. When we compared gene expression profiles between five MM cells and their multidrug-resistant (MM DX) sublines, we found that MM DX cells expressed both SCF and c-Kit and had higher mRNA levels of Slug. Knockdown of c-Kit or Slug expression with their respective small interfering RNA sensitized MM DX cells to the induction of apoptosis by different chemotherapeutic agents, including doxorubicin, paclitaxel, and vincristine. Transfection of c-Kit in parental MM cells in the presence of SCF up-regulated Slug and increased resistance to the chemotherapeutic agents. Moreover, MM cells expressing Slug showed a similar increased resistance to the chemotherapeutic agents. These results indicate that induction of Slug by autocrine production of SCF and c-Kit activation plays a key role in conferring a broad spectrum chemoresistance on MM cells and reveal a novel signal transduction pathway for pharmacological or genetic intervention of MM patients.
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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/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil,
http://linkedlifedata.com/resource/pubmed/chemical/Vincristine,
http://linkedlifedata.com/resource/pubmed/chemical/snail family transcription factors
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
46706-14
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15337769-Apoptosis,
pubmed-meshheading:15337769-Cell Line, Tumor,
pubmed-meshheading:15337769-Cell Separation,
pubmed-meshheading:15337769-Culture Media, Conditioned,
pubmed-meshheading:15337769-Cytokines,
pubmed-meshheading:15337769-DNA, Complementary,
pubmed-meshheading:15337769-Disease Progression,
pubmed-meshheading:15337769-Dose-Response Relationship, Drug,
pubmed-meshheading:15337769-Down-Regulation,
pubmed-meshheading:15337769-Doxorubicin,
pubmed-meshheading:15337769-Drug Resistance, Multiple,
pubmed-meshheading:15337769-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15337769-Flow Cytometry,
pubmed-meshheading:15337769-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15337769-Humans,
pubmed-meshheading:15337769-Immunoblotting,
pubmed-meshheading:15337769-Immunoprecipitation,
pubmed-meshheading:15337769-Lung Neoplasms,
pubmed-meshheading:15337769-Mesothelioma,
pubmed-meshheading:15337769-Paclitaxel,
pubmed-meshheading:15337769-Phenotype,
pubmed-meshheading:15337769-Plasmids,
pubmed-meshheading:15337769-Protein-Tyrosine Kinases,
pubmed-meshheading:15337769-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:15337769-RNA, Small Interfering,
pubmed-meshheading:15337769-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15337769-Signal Transduction,
pubmed-meshheading:15337769-Stem Cell Factor,
pubmed-meshheading:15337769-Transcription Factors,
pubmed-meshheading:15337769-Transfection,
pubmed-meshheading:15337769-Up-Regulation,
pubmed-meshheading:15337769-Verapamil,
pubmed-meshheading:15337769-Vincristine
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pubmed:year |
2004
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pubmed:articleTitle |
Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells.
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pubmed:affiliation |
Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona 60131, Italy. catgfp@yahoo.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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