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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1999-11-18
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pubmed:abstractText |
Activation of the N-ras gene by point mutation occurs in about 15% of all human melanomas. In recently established severe combined immunodeficiency (SCID) mouse xenotransplantation models for human melanoma, we demonstrated that mutated N-ras not only contributes to tumour growth by enhancing cellular proliferation, but also by blocking apoptosis. Mutated N-ras overexpression protected human melanomas from naturally occurring apoptosis and, in a more pronounced way, from chemotherapy-induced apoptosis in vitro and in vivo. Given the potential clinical importance of these findings we sought to determine the underlying mechanism. We found that mutated N-ras specifically upregulates the expression of the anti-apoptosis gene bcl-2 in two human melanoma cell lines in vitro and in SCID mice. Neither the expression of the anti-apoptotic protein Bcl-xL nor that of the pro-apoptotic proteins Bax and Bak were altered in cells expressing mutated N-Ras. The increase in Bcl-2 expression mediated by mutated ras therefore qualifies as a rational explanation for the enhanced chemoresistance of human melanoma expressing mutated N-Ras.
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pubmed:commentsCorrections |
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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/BAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0960-8931
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
347-50
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10504052-Animals,
pubmed-meshheading:10504052-Apoptosis,
pubmed-meshheading:10504052-Blotting, Western,
pubmed-meshheading:10504052-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10504052-Genes, ras,
pubmed-meshheading:10504052-Humans,
pubmed-meshheading:10504052-Melanoma,
pubmed-meshheading:10504052-Membrane Proteins,
pubmed-meshheading:10504052-Mice,
pubmed-meshheading:10504052-Mice, SCID,
pubmed-meshheading:10504052-Neoplasm Transplantation,
pubmed-meshheading:10504052-Point Mutation,
pubmed-meshheading:10504052-Proto-Oncogene Proteins,
pubmed-meshheading:10504052-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10504052-Transfection,
pubmed-meshheading:10504052-Tumor Cells, Cultured,
pubmed-meshheading:10504052-Up-Regulation,
pubmed-meshheading:10504052-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:10504052-bcl-2-Associated X Protein,
pubmed-meshheading:10504052-bcl-X Protein
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pubmed:year |
1999
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pubmed:articleTitle |
Mutated N-ras upregulates Bcl-2 in human melanoma in vitro and in SCID mice.
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pubmed:affiliation |
Institute of Biochemistry, University of Fribourg, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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