Source:http://linkedlifedata.com/resource/pubmed/id/10913157
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
41
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| pubmed:dateCreated |
2000-11-13
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| pubmed:databankReference | |
| pubmed:abstractText |
Although ectopic expression of the cholecystokinin B/gastrin receptor (CCK-BR) is widely reported in human colorectal cancers, its role in mediating the proliferative effects of gastrin1-17 (G-17) on these cancers is unknown. Here we report the isolation of a novel splice variant of CCK-BR that exhibits constitutive (ligand-independent) activation of pathways regulating intracellular free Ca(2+) ([Ca(2+)](i)) and cell growth. The splice variant (designated CCK-BRi4sv for intron 4-containing splice variant) is expressed in colorectal cancers but not in normal colonic mucosa adjacent to the cancer. Balb3T3 cells expressing CCK-BRi4sv exhibited spontaneous, ligand-independent, oscillatory increases in [Ca(2+)](i), whereas cells expressing wild-type CCK-BR did not. Primary cultures of cells isolated from resected colorectal cancers also exhibited a similar pattern of spontaneous [Ca(2+)](i) oscillations. For both Balb3T3 and primary tumor cells, application of G-17 (10 and 200 nm, respectively) caused an increase in [Ca(2+)](i). Selective CCK-BR antagonists blocked the G-17-stimulated Ca(2+) responses but not the spontaneous [Ca(2+)](i) oscillations. Cells expressing CCK-BRi4sv exhibited an increased growth rate ( approximately 2.5-fold), in the absence of G-17, compared with cells expressing wild-type CCK-BR. The selective pattern of expression, constitutive activity, and trophic action associated with CCK-BRi4sv suggest that this variant may regulate colorectal cancer cell proliferation though a gastrin-independent mechanism.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Gastrins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cholecystokinin B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cholecystokinin,
http://linkedlifedata.com/resource/pubmed/chemical/gastrin 17
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
13
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| pubmed:volume |
275
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
32122-8
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:10913157-3T3 Cells,
pubmed-meshheading:10913157-Alternative Splicing,
pubmed-meshheading:10913157-Amino Acid Sequence,
pubmed-meshheading:10913157-Animals,
pubmed-meshheading:10913157-Base Sequence,
pubmed-meshheading:10913157-Binding, Competitive,
pubmed-meshheading:10913157-Calcium,
pubmed-meshheading:10913157-Calcium Signaling,
pubmed-meshheading:10913157-Cell Division,
pubmed-meshheading:10913157-Cloning, Molecular,
pubmed-meshheading:10913157-Colorectal Neoplasms,
pubmed-meshheading:10913157-Female,
pubmed-meshheading:10913157-Gastrins,
pubmed-meshheading:10913157-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10913157-Humans,
pubmed-meshheading:10913157-Introns,
pubmed-meshheading:10913157-Male,
pubmed-meshheading:10913157-Mice,
pubmed-meshheading:10913157-Molecular Sequence Data,
pubmed-meshheading:10913157-Neoplasm Staging,
pubmed-meshheading:10913157-Receptor, Cholecystokinin B,
pubmed-meshheading:10913157-Receptors, Cholecystokinin,
pubmed-meshheading:10913157-Tumor Cells, Cultured
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| pubmed:year |
2000
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| pubmed:articleTitle |
Human colorectal cancers express a constitutively active cholecystokinin-B/gastrin receptor that stimulates cell growth.
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| pubmed:affiliation |
Departments of Surgery, Physiology and Biophysics, and Internal Medicine, the University of Texas Medical Branch, Galveston, Texas 77555, USA. mhellmic@utmb.edu
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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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