Source:http://linkedlifedata.com/resource/pubmed/id/10554023
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
1999-12-2
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pubmed:abstractText |
The introduction of a discontinuous approximately 70-cM portion of human chromosome 17 significantly suppresses the metastatic ability of AT6.1 rat prostate cancer cells without affecting tumorigenicity (M. A. Chekmareva et al., Prostate, 33: 271-280, 1997). We have recently demonstrated that AT6.1 cells containing the approximately 70-cM region (AT6.1-17-4 cells) escape from the primary tumor and arrest in the lung but are growth-inhibited unless the metastasis suppressor region is lost (M. A. Chekmareva et al., Cancer Res., 58: 4963-4969, 1998). A series of in vivo studies indicated that the observed growth inhibition was due to the effect of a gene(s) at the metastatic site (M. A. Chekmareva et al., Cancer Res., 58: 4963-4969, 1998). We have now identified the mitogen-activated protein kinase kinase 4/stress-activated protein/Erk kinase 1 (MKK4/SEK1) gene as a candidate metastasis suppressor gene encoded by the approximately 70-cM region. AT6.1 cells were transfected with a MKK4/SEK1 expression construct, and the cells were tested in standard spontaneous metastasis assays. Whereas the metastatic ability of the AT6.1-MKK4/SEK1 cells was significantly reduced as compared with that of transfection controls, the growth rate of the primary tumors was not affected; the average tumor volume at day 29 after injection was approximately 2 cm. Furthermore, histological examination of the lungs of AT6.1-MKK4/SEK1 tumor-bearing animals revealed that the suppression by MKK4/SEK1 is due to an effect at the metastatic site, consistent with the phenotype conferred by the original approximately 70-cM chromosomal region. These studies implicate MKK4/SEK1 as a metastasis suppressor gene encoded by human chromosome 17.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Map2k4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5483-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10554023-Animals,
pubmed-meshheading:10554023-Chromosomes, Human, Pair 17,
pubmed-meshheading:10554023-DNA, Complementary,
pubmed-meshheading:10554023-Genes, Tumor Suppressor,
pubmed-meshheading:10554023-Humans,
pubmed-meshheading:10554023-Lung,
pubmed-meshheading:10554023-MAP Kinase Kinase 4,
pubmed-meshheading:10554023-Male,
pubmed-meshheading:10554023-Mice,
pubmed-meshheading:10554023-Mice, SCID,
pubmed-meshheading:10554023-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:10554023-Neoplasm Metastasis,
pubmed-meshheading:10554023-Phenotype,
pubmed-meshheading:10554023-Prostatic Neoplasms,
pubmed-meshheading:10554023-Protein-Tyrosine Kinases,
pubmed-meshheading:10554023-Rats,
pubmed-meshheading:10554023-Transfection,
pubmed-meshheading:10554023-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Mitogen-activated protein kinase kinase 4/stress-activated protein/Erk kinase 1 (MKK4/SEK1), a prostate cancer metastasis suppressor gene encoded by human chromosome 17.
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pubmed:affiliation |
Department of Surgery, University of Chicago, Illinois 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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