Source:http://linkedlifedata.com/resource/pubmed/id/10825148
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2000-6-13
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| pubmed:abstractText |
Aberrant signal transduction pathways involved in the development of metastatic disease are poorly defined in both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Neuropeptide-driven positive feedback loops stimulating cell proliferation are characteristic of SCLC. The activation of phospholipase C (PLC)-beta1 is an early and common response to stimulation of G protein-coupled receptors by these neuroendocrine growth factors. The importance of PLC-beta in neuropeptide signaling prompted us to compare PLC-beta isoform expression and activity in four independent SCLC cell lines and four independent NSCLC cell lines. We found that PLC-beta1 is more highly expressed in SCLC than in NSCLC, as indicated by Western blotting of cell lysates. All SCLC lines studied express PLC-beta1; only one of the NSCLC lines investigated showed detectable levels of the enzyme. NSCLC lines are significantly more sensitive to the antiproliferative effects of ET-18-OCH3 (edelfosine) compared with the SCLC lines, as indicated by [3H]thymidine uptake. The only SCLC cell line (NCI-H345) that is as sensitive as the NSCLC cell lines to ET-18-OCH3 also expresses uniquely low levels of PLC-beta1. The participation of PLC-beta1 in signaling by SCLC growth factor receptors is indicated by our finding that PLC-beta1 (but not PLC-beta3) coimnunoprecipitates with G(alpha)q/11 upon activation of neurotensin receptors; this association is inhibited by ET-18-OCH3. Ca2+ mobilization mediated by neurotensin receptors is also inhibited by ET-18-OCH3. The binding of GTPgammaS to G(alpha)q/11 upon treatment of SCLC cells with neurotensin is not inhibited by ET-18-OCH3. These findings indicate that ET-18-OCH3 does not interfere with G(alpha)q/11 activation but rather inhibits the association of G(alpha)q/11 with PLC-beta1. Our data suggest that PLC-beta is an important mediator of both SCLC and NSCLC proliferation. Differences in PLC-beta1 expression may be exploitable in the development of effective diagnostic and therapeutic tools.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/PLCB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PLCB3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C beta,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipid Ethers,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/edelfosine
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
60
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2730-6
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10825148-Antineoplastic Agents,
pubmed-meshheading:10825148-Calcium,
pubmed-meshheading:10825148-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:10825148-Carcinoma, Small Cell,
pubmed-meshheading:10825148-Drug Resistance, Neoplasm,
pubmed-meshheading:10825148-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:10825148-GTP-Binding Proteins,
pubmed-meshheading:10825148-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:10825148-Humans,
pubmed-meshheading:10825148-Isoenzymes,
pubmed-meshheading:10825148-Lung Neoplasms,
pubmed-meshheading:10825148-Phosphodiesterase Inhibitors,
pubmed-meshheading:10825148-Phospholipase C beta,
pubmed-meshheading:10825148-Phospholipid Ethers,
pubmed-meshheading:10825148-Tumor Cells, Cultured,
pubmed-meshheading:10825148-Type C Phospholipases
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| pubmed:year |
2000
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| pubmed:articleTitle |
Small cell lung carcinoma exhibits greater phospholipase C-beta1 expression and edelfosine resistance compared with non-small cell lung carcinoma.
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| pubmed:affiliation |
Molecular Pharmacology Laboratory, Guthrie Research Institute, Syre, Pennsylvania 18840, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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