Linked Life Data

9004036

Source:http://linkedlifedata.com/resource/pubmed/id/9004036

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-3-25
pubmed:abstractText
Cell adhesion molecules are not only required for maintenance of tissue integrity, but also regulate many aspects of cell behaviour, including growth and differentiation. While the regulatory functions of integrin extracellular matrix receptors in keratinocytes are well established, such functions have not been investigated for the primary receptors that mediate keratinocyte intercellular adhesion, the cadherins. To examine cadherin function in normal human epidermal keratinocytes we used a retroviral vector to introduce a dominant negative E-cadherin mutant, consisting of the extracellular domain of H-2Kd and the transmembrane and cytoplasmic domains of E-cadherin. As a control a vector containing the same construct, but with the catenin binding site destroyed, was prepared. High levels of expression of the constructs were achieved; the dominant negative mutant, but not the control, formed complexes with alpha-, beta- and gamma-catenin. In cells expressing the dominant negative mutant there was a 5-fold decrease in the level of endogenous cadherins and a 3-fold increase in the level of beta-catenin. Cell-cell adhesion and stratification were inhibited by the dominant negative mutant and desmosome formation was reduced. Expression of the mutant resulted in reduced levels of the alpha 2 beta 1 and alpha 3 beta 1 integrins and increased cell motility, providing further evidence for cross-talk between cadherins and the beta 1 integrins. In view of the widely documented loss of E-cadherin in keratinocyte tumours it was surprising that the dominant negative mutant had an inhibitory effect on keratinocyte proliferation and stimulated terminal differentiation even under conditions in which intercellular adhesion was prevented. These results establish a role for cadherins in regulating keratinocyte growth and differentiation and raise interesting questions as to the relative importance of cell adhesion-dependent and -independent mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CTNNA1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cadherins, http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Desmoplakins, http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens, http://linkedlifedata.com/resource/pubmed/chemical/H-2K(K) antigen, http://linkedlifedata.com/resource/pubmed/chemical/Integrins, http://linkedlifedata.com/resource/pubmed/chemical/JUP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/alpha Catenin, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin, http://linkedlifedata.com/resource/pubmed/chemical/gamma Catenin
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
109 ( Pt 13)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3013-23
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes.
pubmed:affiliation
Keratinocyte Laboratory, Imperial Cancer Research Fund, London, UK.
pubmed:publicationType
Journal Article