Document Detail


Antiproliferative actions of growth hormone-releasing hormone antagonists on MiaPaCa-2 human pancreatic cancer cells involve cAMP independent pathways.
MedLine Citation:
PMID:  11390017     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluated the effects of GHRH antagonists on the proliferation of MiaPaCa-2 human pancreatic cancer cells and cAMP signaling in vitro. GHRH antagonists inhibited the proliferation of MiaPaCa-2 cells in vitro in a dose-dependent way and caused a significant elevation in cAMP production. In a superfusion system, short-term exposure of the cells to GHRH antagonists evoked an acute, dose-dependent release of cAMP into the medium. Native GHRH, which stimulates cAMP efflux from pituitary at nanomolar doses, did not influence cAMP release from cultured or superfused MiaPaCa-2 cells even at 10-30 microM. VIP, PACAP, secretin and glucagon also did not influence cell proliferation or cAMP production. Adenylate cyclase activator forskolin (FSK) caused a greater cAMP response, but a smaller antiproliferative effect than GHRH antagonists. Combined treatment with FSK and GHRH antagonist JV-1-38 potentiated the cAMP-inducing effect of FSK, but did not produce a greater inhibition of cell proliferation than JV-1-38 alone. A selective accumulation of radiolabeled GHRH antagonist [(125)I]JV-1-42 in vivo in MiaPaCa-2 carcinoma xenografted into nude mice was also observed. In conclusion, second messengers other than cAMP participate in the signal transduction pathways of GHRH analogs mediated by tumoral GHRH receptors.
Authors:
Z Rekasi; J L Varga; A V Schally; A Plonowski; G Halmos; B Csernus; P Armatis; K Groot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Peptides     Volume:  22     ISSN:  0196-9781     ISO Abbreviation:  Peptides     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-06     Completed Date:  2001-08-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008690     Medline TA:  Peptides     Country:  United States    
Other Details:
Languages:  eng     Pagination:  879-86     Citation Subset:  IM    
Affiliation:
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Animals
Cell Division / drug effects
Cyclic AMP / metabolism*
Dose-Response Relationship, Drug
Forskolin / pharmacology
Glucagon / pharmacology
Growth Hormone-Releasing Hormone / antagonists & inhibitors*
Humans
Male
Mice
Mice, Nude
Muscles / metabolism
Neoplasm Transplantation
Neuropeptides / pharmacology
Pancreatic Neoplasms / metabolism*
Pituitary Adenylate Cyclase-Activating Polypeptide
Radioimmunoassay
Secretin / pharmacology
Signal Transduction
Tumor Cells, Cultured
Vasoactive Intestinal Peptide / pharmacology
Chemical
Reg. No./Substance:
0/ADCYAP1 protein, human; 0/Adcyap1 protein, mouse; 0/Neuropeptides; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 1393-25-5/Secretin; 37221-79-7/Vasoactive Intestinal Peptide; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 9007-92-5/Glucagon; 9034-39-3/Growth Hormone-Releasing Hormone; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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