DOI: 10.1097/01.MPA.0000335488.86507.5b

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Issn Print: 0885-3177

Publication Date: 2008/11/01


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THE EXPRESSION OF LEF-1 IS ABLE TO INDUCE INVERSE REGULATION OF E-CADHERIN AND P-CADHERIN IN PANCREATIC CANCER

A. König; S. Jesse; V. Ellenrieder; T. Gress; A. Menke

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Author Information: Department of Gastroenterology, University of Marburg, Marburg, Germany and

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Excerpt

The regulation of cadherin adhesion modules is crucial for the constitution and functionality of different tissues. The connection of E-cadherin and the actin cytoskeleton results in enhanced intercellular contact and formation of epithelial tissue, while P-cadherin increases mostly cellular motility and supports epithelial to mesenchymal transition (EMT). An inverse regulation of both cadherins, as well as a crucial role of the transcription factor Lef-1 in this regulatory process, could be detected during several processes of EMT in hair development.
In our present work, we can demonstrate that Lef-1 is overexpressed in pancreatic cancer. Additionally, Lef-1 is able to reduce the expression of E-cadherin on protein and RNA-expression levels, using a new splice variant. In contrast, P-cadherin expression levels are elevated in pancreatic cancer. Overexpressed Lef-1 is able to enhance the expression of P-cadherin, which is due to transcriptional activation of the P-cadherin promoter.
The inverse regulation of E- and P-cadherin is probably caused by increased expression of Lef-1, as we could show that in cells with a high expression level of Lef-1 and P-cadherin as well as a marginal expression of E-cadherin (SW480), overexpression of dominant negative Lef-1 (Lef-1 ΔHMG) reduces P-cadherin protein levels and inversely enhances E-cadherin protein levels.
Additionally, pancreatic cancer cells overexpressing Lef-1 - resulting in increased P-cadherin and reduced E-cadherin expression - show a reduced cellular aggregation.

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