Source:http://linkedlifedata.com/resource/pubmed/id/15280446
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2004-7-28
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pubmed:abstractText |
Nucleoside diphosphate kinase A (NDPK-A), encoded by the nm23-H1 gene, acts as a metastasis suppressor in certain human tumors such as breast carcinoma. However, evidence also points to NDPK-A functioning as a metastasis promoter in other human tumors including neuroblastoma. In fact, amplification and overexpression of nm23-H1 as well as S120G mutation of NDPK-A (NDPK-A(S120G)) have been detected in 14% to 30% of patients with advanced stages of neuroblastoma. To test whether NDPK-A promotes neuroblastoma metastasis, we established stable transfectants and an orthotopic xenograft animal model from the human neuroblastoma NB69 cell line. We demonstrate that overexpressed NDPK-A or NDPK-A(S120G) increased both incidence and colonization of neuroblastoma metastasis in animal lungs without significantly affecting primary tumor development. In vitro, these metastasis-associated NDPK-A aberrations abrogated retinoic acid-induced neuronal differentiation while increasing cloning efficiency, cell survival, and colony formation of NB69 derivatives. Furthermore, NDPK-A(S120G) reduced cell adhesion and increased cell migration. Compared with its wild-type, NDPK-A(S120G) appears more effective in promoting neuroblastoma metastasis. Our results provide the first evidence that NDPK-A behaves as a metastasis promoter at least in human neuroblastoma derived from NB69 cells. The findings not only suggest a prognostic value of NDPK-A in neuroblastoma patients but also caution NDPK-A-targeted treatment for patients with different tumor types.
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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/NM23 Nucleoside Diphosphate Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NME1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nme1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside-Diphosphate Kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1541-7786
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
387-94
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15280446-Animals,
pubmed-meshheading:15280446-Cell Adhesion,
pubmed-meshheading:15280446-Cell Differentiation,
pubmed-meshheading:15280446-Cell Line, Tumor,
pubmed-meshheading:15280446-Cell Movement,
pubmed-meshheading:15280446-Cell Proliferation,
pubmed-meshheading:15280446-Cell Survival,
pubmed-meshheading:15280446-Clone Cells,
pubmed-meshheading:15280446-Disease Models, Animal,
pubmed-meshheading:15280446-Humans,
pubmed-meshheading:15280446-Lung Neoplasms,
pubmed-meshheading:15280446-Mice,
pubmed-meshheading:15280446-Mice, SCID,
pubmed-meshheading:15280446-Mutation,
pubmed-meshheading:15280446-NM23 Nucleoside Diphosphate Kinases,
pubmed-meshheading:15280446-Neoplasm Metastasis,
pubmed-meshheading:15280446-Neoplasm Transplantation,
pubmed-meshheading:15280446-Neuroblastoma,
pubmed-meshheading:15280446-Nucleoside-Diphosphate Kinase,
pubmed-meshheading:15280446-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Nucleoside diphosphate kinase A/nm23-H1 promotes metastasis of NB69-derived human neuroblastoma.
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pubmed:affiliation |
Department of Medicine, University of California at San Diego, 4028 Basic Science Building, 9500 Gilman Drive, La Jolla, CA 92093-0688, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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