Document Detail


Role of stimulatory guanine nucleotide binding protein (GSalpha) in proliferation of PC-3M prostate cancer cells.
MedLine Citation:
PMID:  11149419     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have shown that calcitonin-like immunoreactive substances are secreted by primary prostate cells. Furthermore, exogenously added calcitonin stimulates proliferation of androgen-responsive LnCaP cells. To examine the possible effect of calcitonin on growth of invasive prostate cancer cells, we tested its effects on proliferation of PC-3M cells. Calcitonin stimulated DNA synthesis of PC-3M cells in a dose-dependent fashion, and also stimulated adenylyl cyclase and protein kinase C activities. To further delineate the role of these signaling cascades in proliferation of PC-3M prostate cancer cells, we selectively activated these pathways by transfecting cDNAs expressing constitutively active forms of either Gsalpha (Gsalpha-QL) or Gqalpha (Gqalpha-QL). cDNAs expressing wild-type forms of G-proteins (Gsalpha-WT and Gqalpha-WT) were used as vehicle controls. Gqalpha-QL transfectants exhibited growth inhibition and terminal differentiation. Those expressing Gsalpha-QL exhibited a dramatic increase in growth rate. Gsalpha-QL transfectants displayed an almost 3-fold increase in [3H]-thymidine incorporation and over a 4-fold increase in growth rate when compared with parental PC-3M cells or those expressing wild-type Gsalpha (Gsalpha-WT). The growth-promoting action of Gsalpha-QL could not be mimicked by either 8-bromo cAMP or forskolin. However, nifedipine, a calcium channel antagonist, potently and selectively inhibited DNA synthesis in Gsalpha-QL transfectants. These results suggest that the growth-promoting actions of Gsalpha on PC-3M cells may be mediated by nifedipine-sensitive proliferative events.
Authors:
J Chien; G V Shah
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  91     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-01-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  46-54     Citation Subset:  IM    
Affiliation:
Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, USA.
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MeSH Terms
Descriptor/Qualifier:
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Adenylate Cyclase / metabolism
Blotting, Western
Calcitonin / metabolism
Calcium Channel Blockers / pharmacology
Calcium Channels / metabolism
Cell Division / drug effects
Cyclic AMP / metabolism
DNA Replication / drug effects
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Forskolin / pharmacology
GTP-Binding Protein alpha Subunits, Gs / metabolism*,  physiology*
GTP-Binding Proteins / metabolism*,  physiology*
Humans
Male
Nifedipine / pharmacology
Prostatic Neoplasms / metabolism*
Protein Kinase C / metabolism
Signal Transduction
Time Factors
Transfection
Tumor Cells, Cultured
Verapamil / pharmacology
Grant Support
ID/Acronym/Agency:
DK-45044/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels; 21829-25-4/Nifedipine; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 52-53-9/Verapamil; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 9007-12-9/Calcitonin; EC 2.7.11.13/Protein Kinase C; EC 3.6.1.-/GTP-Binding Proteins; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gs; EC 4.6.1.1/Adenylate Cyclase

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


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