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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

N-cadherin-mediated adhesion and aberrant catenin expression in anaplastic thyroid-carcinoma cell lines.

The role of cadherins and catenins in the progression of thyroid carcinoma is unclear. We have investigated alpha-, beta- and gamma-catenins and p120(ctn) in relation to the expression of cadherins in human anaplastic thyroid-carcinoma cell lines (HTh7, HTh74, C643 and SW1736) with Western blotting and immunofluorescence. E-cadherin was lacking except in SW1736, which consisted of E-cadherin-positive (approx. 5%) and -negative cells. The alpha- and beta-catenin levels were similar to those of primary cultured non-neoplastic (E-cadherin-positive) human thyrocytes. In contrast, the expression of gamma-catenin was low and variable, correlating with the different levels of cytokeratin in the same cells (HTh74 > SW1736 > C643 > HTh7). p120(ctn) resolved as a doublet in Western blots; the approximately 100-kDa band also found in non-neoplastic epithelial cells was reduced whereas the approximately 115-kDa band, corresponding to the fibroblast-type isoform of p120(ctn), was neo-expressed. A DNA-demethylating agent, 5-aza-2'-deoxycytidine, up-regulated E-cadherin in SW1736 and gamma-catenin in SW1736 and C643, whereas the other cell lines were unresponsive; other catenins were not affected. The catenins were generally distributed along the cell borders. Immunostaining, cell-surface biotinylation and co-immunoprecipitation revealed that all cell lines expressed N-cadherin in connection with beta-catenin at the plasma membrane. Incubation with an N-cadherin antibody disrupted cell-cell adhesion. We conclude that E-cadherin-negative anaplastic thyroid-carcinoma cell lines display functional N-cadherin/beta-catenin complexes, partial or complete loss of gamma-catenin, and isoform shift of p120(ctn). The unequal expression of E-cadherin and gamma-catenin and the variable response to DNA de-methylation suggest that anaplastic thyroid carcinoma is not a uniform entity.[1]


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