Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-9-16
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
264-8
pubmed:dateRevised
2009-11-19
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
pubmed:year
1996
pubmed:articleTitle
An effect of K-ras gene mutation on epidermal growth factor receptor signal transduction in PANC-1 pancreatic carcinoma cells.
pubmed:affiliation
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
pubmed:publicationType
Journal Article