rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1996-9-16
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pubmed:abstractText |
The Ras protein is involved in tyrosine kinase signal transduction pathway steps such as EGFR signalling. Most human pancreatic carcinomas harbor a point mutation of K-ras oncogene and overexpress transforming TGF-alpha. We studied how K-ras gene mutation could influence the EGFR signal transduction mechanism and the autonomous proliferation of pancreatic carcinoma cells, using PANC-1 human pancreatic carcinoma line and W1-38 normal human fibroblast cell line as a control. PANC-1 cells responded to neither EGF nor exogenous TGF-alpha, although anti-TGF-alpha MAb suppressed their growth. Expression of TGF-alpha mRNA was detected only in PANC-1 cells, which confirmed EGFR being within an autocrine loop. Ras protein and MAP kinase were constitutively activated in PANC-1 cells so that the cells did not respond to treatment with staurosporine or herbimycin A, and exhibited slight response to EGF stimulation. PANC-1 cells harbored K-ras gene mutation in codon 12. In contrast, EGF stimulation induced an elevation of GTP-bound ratio to Ras protein and an activation of MAP kinase with accelerated growth in W1-38 cells. From these findings, we concluded that K-ras gene mutation possibly plays an important role in the autonomous proliferation of PANC-1 pancreatic carcinoma cells, and that an autocrine loop represented by TGF-alpha and EGFR may further accelerate the growth of PANC-1 cells.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0020-7136
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
264-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8760597-Antibodies, Monoclonal,
pubmed-meshheading:8760597-Base Sequence,
pubmed-meshheading:8760597-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:8760597-Enzyme Activation,
pubmed-meshheading:8760597-Enzyme Inhibitors,
pubmed-meshheading:8760597-Epidermal Growth Factor,
pubmed-meshheading:8760597-Genes, ras,
pubmed-meshheading:8760597-Guanine Nucleotides,
pubmed-meshheading:8760597-Humans,
pubmed-meshheading:8760597-Molecular Sequence Data,
pubmed-meshheading:8760597-Mutation,
pubmed-meshheading:8760597-Pancreatic Neoplasms,
pubmed-meshheading:8760597-Phosphotyrosine,
pubmed-meshheading:8760597-RNA, Messenger,
pubmed-meshheading:8760597-Receptor, Epidermal Growth Factor,
pubmed-meshheading:8760597-Signal Transduction,
pubmed-meshheading:8760597-Transforming Growth Factor alpha,
pubmed-meshheading:8760597-Tumor Cells, Cultured,
pubmed-meshheading:8760597-ras Proteins
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pubmed:year |
1996
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pubmed:articleTitle |
An effect of K-ras gene mutation on epidermal growth factor receptor signal transduction in PANC-1 pancreatic carcinoma cells.
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pubmed:affiliation |
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
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pubmed:publicationType |
Journal Article
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