Document Detail


Alpha integrin subunits regulate human (Caco-2) intestinal epithelial proliferation and phenotype.
MedLine Citation:
PMID:  10844395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Cell-matrix interactions influence intestinal epithelial biology, but the whether specific integrin heterodimers exert different effects is unclear. METHODS: We used functional antibodies to investigate effects of the alpha2, alpha3, alpha5, and alpha6 integrin subunits on proliferation and differentiation of human intestinal Caco-2 cells on laminin. Cells seeded onto laminin-coated inserts in defibronectinized medium were treated with functional antibodies or normal IgG for 72 hrs and proliferation, alkaline phosphatase and dipeptidyl dipeptidase specific activity were measured. RESULTS: Caco-2 adhesion to antibody to each alpha-integrin subunit stimulated tyrosine phosphorylation of Focal Adhesion Kinase and paxillin, suggesting that these antibodies intiate integrin-related tyrosine signalling. Proliferation was inhibited by anti-alpha2 and anti-alpha3, but stimulated by anti-alpha6. Alkaline phosphatase and dipeptidyl dipeptidase specific activity were promoted by alpha2 blockade but decreased after a6 blockade. Proliferative blockade using mitomycin C or hydroxyurea prevented the effects of alpha2 ligation on differentiation, but the decrease in alkaline phosphatase specific activity observed after a6 integrin subunit blockade was preserved even after proliferative blockade. CONCLUSION: lntegrin heterodimers modulate human Caco-2 intestinal epithelial biology on laminin in an alpha-subunit specific manner. The different effects of anti-alpha2 and anti-alpha6 may reflect competitition by these antibodies with integrin subunit interactions with laminin as well as initiation of their own signals or different functions for the alpha6 integrin subunit
Authors:
M D Basson; N J Emenaker; M A Sanders
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  10     ISSN:  1015-8987     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2000  
Date Detail:
Created Date:  2000-07-20     Completed Date:  2000-07-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  27-36     Citation Subset:  IM    
Affiliation:
Depts. of Surgery, Yale University School of Medicine and CT VA Health Care System, New Haven and West Haven, CT 06520, USA. marc.basson@yale.edu
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MeSH Terms
Descriptor/Qualifier:
Antibodies / immunology
Caco-2 Cells
Cell Division / physiology*
Epithelial Cells / cytology
Humans
Integrins / immunology,  physiology*
Intestines / cytology*
Phenotype
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
R29DK47051/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Integrins

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


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