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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0032005,
umls-concept:C0033713,
umls-concept:C0040648,
umls-concept:C0085828,
umls-concept:C0087140,
umls-concept:C0162508,
umls-concept:C0185117,
umls-concept:C0235974,
umls-concept:C1305923,
umls-concept:C1515877,
umls-concept:C1518174,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
3
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pubmed:dateCreated |
1997-3-18
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pubmed:abstractText |
Pituitary adenylate-cyclase-activating polypeptide (PACAP) has been shown to possess mitogenic activity in various tumor cells. The present study was designed to investigate signal transduction mechanisms and expression of the proto-oncogenes c-fos and c-jun linked to the mitogenic effect of PACAP in the pancreatic carcinoma cell line AR4-2J. PACAP-(1-27)-peptide and PACAP-(1-38)-peptide, but not the structurally related vasoactive intestinal polypeptide (VIP), potently stimulated [3H]thymidine incorporation and cell number at doses of 0.1-10 nM. Both molecular forms of PACAP strongly increased formation of cAMP and inositol trisphosphate, elevated cytosolic Ca2+ levels and induced mitogen-activated protein (MAP) kinase activity. Quantitative reverse-transcription PCR revealed that PACAP-(1-27)-peptide and PACAP-(1-38)-peptide elevated c-fos mRNA levels 50-100-fold, whereas c-jun mRNA levels increased only moderately (2-3-fold). The effect of PACAP on c-fos and c-jun expression in AR4-2J cells was rapid (20 min), transient (1-2 h), dose-dependent IC50, 0.5 nM) and was abolished by the specific PACAP receptor antagonist PACAP-(6-38)-peptide or inhibitors of protein kinase C or tyrosine kinases. Compared with PACAP, epidermal growth factor and gastrin equipotently stimulated c-fos transcription whereas VIP, secretin, forskolin or phorbolester showed only marginal effects. Both PACAP (1-27)-peptide and PACAP-(1-38)-peptide strongly increased the DNA binding activity of the c-fos/ c-jun heterodimer transcription factor AP-1 at 10 nM and also stimulated AP-1 transcriptional activity up to 20-fold in AR4-2J cells. These findings indicate that the mitogenic effect of PACAP mediated via activation of the GTP-binding protein coupled PACAP/VIP-1 (PV1) receptor is linked to the MAP kinase cascade, increased expression of the proto-oncogenes c-fos and c-jun and activation of the heterodimeric transcription factor AP-1.
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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/Adcyap1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pituitary Adenylate...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/W 7
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0014-2956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
242
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
467-76
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9022670-Animals,
pubmed-meshheading:9022670-Calcium,
pubmed-meshheading:9022670-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9022670-Cell Cycle,
pubmed-meshheading:9022670-Cyclic AMP,
pubmed-meshheading:9022670-Cytosol,
pubmed-meshheading:9022670-Enzyme Inhibitors,
pubmed-meshheading:9022670-Gene Expression Regulation,
pubmed-meshheading:9022670-Genes, fos,
pubmed-meshheading:9022670-Genes, jun,
pubmed-meshheading:9022670-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:9022670-Mitogens,
pubmed-meshheading:9022670-Neuropeptides,
pubmed-meshheading:9022670-Pituitary Adenylate Cyclase-Activating Polypeptide,
pubmed-meshheading:9022670-Protein Kinase C,
pubmed-meshheading:9022670-Protein-Tyrosine Kinases,
pubmed-meshheading:9022670-RNA, Messenger,
pubmed-meshheading:9022670-Rats,
pubmed-meshheading:9022670-Signal Transduction,
pubmed-meshheading:9022670-Sulfonamides,
pubmed-meshheading:9022670-Transcription Factor AP-1
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pubmed:year |
1996
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pubmed:articleTitle |
Pituitary adenylate-cyclase-activating polypeptide stimulates proto-oncogene expression and activates the AP-1 (c-Fos/c-Jun) transcription factor in AR4-2J pancreatic carcinoma cells.
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pubmed:affiliation |
1st Department of Medicine, Christian-Albrechts University, Kiel, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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