Document Detail


Connexin43 increases the sensitivity of prostate cancer cells to TNFalpha-induced apoptosis.
MedLine Citation:
PMID:  17200141     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To examine the effects of increased expression of connexin43 (Cx43) upon cell viability and response to cytotoxic agents, we expressed Cx43 in LNCaP and PC3 prostate cancer cells by infection with a recombinant adenovirus (Ad-Cx43). Infection with Ad-Cx43 led to the formation of Cx43-containing gap junction plaques at appositional membranes and increased Lucifer Yellow transfer in LNCaP cells, but not in PC3 cells. The increased intercellular communication was blocked by co-infection with an adenovirus containing a dominant-negative Cx43 (Ad-Cx43DN). Infection of LNCaP (but not PC3) cells with Ad-Cx43 greatly increased their sensitivity to killing by tumor necrosis factor alpha (TNFalpha), anti-Fas antibodies, and TRAIL as quantified using an MTS assay. The TNFalpha-induced cell death was dependent on cell density, and it was associated with increased annexin V staining, an increased proportion of sub-G1 cells, and activation of caspase 8. The TNFalpha-induced effects on Ad-Cx43-infected LNCaP cells were blocked by co-infection with Ad-Cx43DN or by pre-incubation with neutralizing antibodies directed against TNFalpha receptor 1. These results demonstrate that TNFalpha induces apoptosis in LNCaP cells by signaling through TNFalpha receptor 1 and that expression of functional Cx43 gap junction channels increases their sensitivity to TNFalpha.
Authors:
Min Wang; Viviana M Berthoud; Eric C Beyer
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-01-02
Journal Detail:
Title:  Journal of cell science     Volume:  120     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-04-11     Revised Date:  2013-05-13    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  320-9     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Section of Hematology/Oncology and Stem Cell Transplantation, University of Chicago, Chicago, IL 60637, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / metabolism
Annexin A5 / metabolism
Apoptosis / drug effects*
Caspase 8 / metabolism
Cell Line, Tumor
Cell Survival / drug effects
Connexin 43 / genetics,  metabolism*
Enzyme Activation / drug effects
Fluorescein-5-isothiocyanate
Fluorescent Antibody Technique, Indirect
Fluorescent Dyes
Humans
Kinetics
Male
Propidium
Prostatic Neoplasms / pathology
Recombinant Proteins / metabolism,  pharmacology
Tumor Necrosis Factor-alpha / genetics,  metabolism*,  pharmacology
Grant Support
ID/Acronym/Agency:
HL59199/HL/NHLBI NIH HHS; R01 HL045466/HL/NHLBI NIH HHS; R01 HL059199/HL/NHLBI NIH HHS; R01 HL059199-07/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Connexin 43; 0/Fluorescent Dyes; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 3326-32-7/Fluorescein-5-isothiocyanate; 36015-30-2/Propidium; EC 3.4.22.-/Caspase 8
Comments/Corrections

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