Source:http://linkedlifedata.com/resource/pubmed/id/20213325
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2010-4-2
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| pubmed:abstractText |
The present study investigated the intracellular regulation of E-cadherin in ovarian carcinoma. E-cadherin expression and regulation by Snail and Pak1 were studied in ES-2 and OVCAR-3 ovarian cancer cells in vitro. Twist1, Zeb1 and Vimentin mRNA expression and HIF-1alpha protein expression were analyzed in 80 and 189 clinical specimens, respectively. OVCAR-3 cells incubated with an anti-E-cadherin antibody formed smaller and looser spheroids compared to controls. Snail silencing using Small Hairpin RNA in ES-2 cells reduced invasion and MMP-2 activity, with unaltered cellular morphology. Using dominant negative (DN) and constitutively active (CA) Pak1 constructs, we found that DN Pak1 ES-2 and OVCAR-3 clones had reduced attachment to matrix proteins, invasion and MMP-2 activity compared to CA and wild-type cells. DN Pak1 ES-2 cells also bound less to LP9 mesothelial cells. DN Pak1 OVCAR-3 cells had lower Vimentin levels. Snail expression was lower in cultured effusions compared to primary carcinomas, and was cytoplasmic rather than nuclear. Twist1 (P < 0.001), Zeb1 (P = 0.003) and Vimentin (P = 0.03) mRNA expression was significantly higher in solid metastases compared to primary carcinomas and effusions. HIF-1alpha protein expression was lower in effusions compared to primary carcinomas and solid metastases (P = 0.033). Our data suggest that the previously reported E-cadherin re-expression in ovarian carcinoma effusions is regulated by Pak1. The transient nature of E-cadherin expression during ovarian carcinoma progression is probably the result of partial epithelial-to-mesenchymal transition (EMT) and the reverse process of mesenchymal-to-epithelial-like transition (MET). Expression of the EMT-related molecules Twist, Zeb1, Vimentin and HIF-1alpha is anatomic site-dependent in ovarian carcinoma.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TWIST1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Twist Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Vimentin,
http://linkedlifedata.com/resource/pubmed/chemical/ZEB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/p21-Activated Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/snail family transcription factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1573-7276
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
27
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
161-72
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| pubmed:dateRevised |
2010-7-8
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| pubmed:meshHeading |
pubmed-meshheading:20213325-Base Sequence,
pubmed-meshheading:20213325-Cadherins,
pubmed-meshheading:20213325-Cell Line, Tumor,
pubmed-meshheading:20213325-Epithelial Cells,
pubmed-meshheading:20213325-Epithelium,
pubmed-meshheading:20213325-Female,
pubmed-meshheading:20213325-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20213325-Homeodomain Proteins,
pubmed-meshheading:20213325-Humans,
pubmed-meshheading:20213325-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:20213325-Mesoderm,
pubmed-meshheading:20213325-Nuclear Proteins,
pubmed-meshheading:20213325-Ovarian Neoplasms,
pubmed-meshheading:20213325-Pleural Effusion, Malignant,
pubmed-meshheading:20213325-RNA, Messenger,
pubmed-meshheading:20213325-Transcription Factors,
pubmed-meshheading:20213325-Twist Transcription Factor,
pubmed-meshheading:20213325-Vimentin,
pubmed-meshheading:20213325-p21-Activated Kinases
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| pubmed:year |
2010
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| pubmed:articleTitle |
Mesenchymal-to-epithelial transition determinants as characteristics of ovarian carcinoma effusions.
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| pubmed:affiliation |
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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