Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0007603,
umls-concept:C0007634,
umls-concept:C0035339,
umls-concept:C0035820,
umls-concept:C0105770,
umls-concept:C0442805,
umls-concept:C0475264,
umls-concept:C0808080,
umls-concept:C1154382,
umls-concept:C1512505,
umls-concept:C1705922,
umls-concept:C2261503,
umls-concept:C2350440
|
| pubmed:issue |
8
|
| pubmed:dateCreated |
1996-12-18
|
| pubmed:abstractText |
In this study we show that a breast cancer cell line (SKBR3) that expresses no E-cadherin and very low levels of beta-catenin protein and exhibits a poorly adhesive phenotype in Matrigel responds to retinoic acid (RA) by a marked increase in epithelial differentiation. Specifically, treatment of cells with all-trans-RA, 9-cis-RA, or a RA receptor alpha-specific ligand resulted in a large increase in cell-cell adhesive strength and stimulated the formation of fused cell aggregates in Matrigel. A retinoid X receptor-specific ligand was ineffective. Exposure of cells to 9-cis-RA for as little as 4 h was sufficient to maintain the adhesive phenotype for at least 4 days. The effects of 9-cis-RA required protein and RNA synthesis, but were not mediated by factors secreted by stimulated cells or by direct cell contact and did not require serum. These 9-cis-RA-induced morphological effects were completely reversed by growing cells in 50 microM Ca2+, suggesting a mechanism involving a 9-cis-RA-induced increase in Ca(2+)-dependent adhesion. Consistent with this, beta-catenin protein levels were markedly elevated in the 9-cis-RA-treated cells, and beta-catenin became localized to a Triton-insoluble pool at regions of cell-cell contact. No change could be detected in beta-catenin steady state messenger RNA levels, but 9-cis-RA did increase beta-catenin protein stability. Treatment of cells with low calcium medium did not prevent the 9-cis-RA-induced increase in total beta-catenin protein, but did prevent its movement to a Triton-insoluble pool at the cell membrane. Among several kinase inhibitors, only the broad spectrum kinase inhibitor staurosporine and the protein kinase C inhibitor bisindoylmaleimide reversed the morphological changes induced by 9-cis-RA. Like treatment with low calcium medium, these inhibitors did not prevent the 9-cis-RA-induced increase in total beta-catenin protein levels, but completely prevented the movement of beta-catenin to the cell membrane. These results point to a role for beta-catenin and serine kinase activity in mediating the action of 9-cis-RA in epithelial differentiation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0013-7227
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
137
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3265-73
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8754749-Breast Neoplasms,
pubmed-meshheading:8754749-Cadherins,
pubmed-meshheading:8754749-Calcium,
pubmed-meshheading:8754749-Cell Adhesion,
pubmed-meshheading:8754749-Cell Differentiation,
pubmed-meshheading:8754749-Cell Membrane,
pubmed-meshheading:8754749-Culture Media,
pubmed-meshheading:8754749-Cytoskeletal Proteins,
pubmed-meshheading:8754749-Drug Stability,
pubmed-meshheading:8754749-Epithelium,
pubmed-meshheading:8754749-Female,
pubmed-meshheading:8754749-Humans,
pubmed-meshheading:8754749-Indoles,
pubmed-meshheading:8754749-Maleimides,
pubmed-meshheading:8754749-Protein-Serine-Threonine Kinases,
pubmed-meshheading:8754749-RNA, Messenger,
pubmed-meshheading:8754749-Staurosporine,
pubmed-meshheading:8754749-Tissue Distribution,
pubmed-meshheading:8754749-Trans-Activators,
pubmed-meshheading:8754749-Tretinoin,
pubmed-meshheading:8754749-Tumor Cells, Cultured,
pubmed-meshheading:8754749-beta Catenin
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Retinoids increase cell-cell adhesion strength, beta-catenin protein stability, and localization to the cell membrane in a breast cancer cell line: a role for serine kinase activity.
|
| pubmed:affiliation |
Department of Cell Biology, Georgetown University Medical Center, Washington D.C.20007, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|