| Popis: |
E-cadherin belongs to the cadherins,which constitute a large family of calcium-dependent cell adhesion molecules. Cell-to-cell adhesion plays a critical role in the development and maintaince of complex differentiated epithelial tissues and structures in multicellular organisms. Interference with cell attachment, independence of growth control, and increased migration have long been implicated during the neoplastic process. It is now apparent that the hallmarks of epithelial malignancy, that is to say, uncontroled proliferation, derangement of cellular and morphological differentiation, invasion, and colonisation to distant organs, can be explained, at least in part, by alteration in the adhesive properties of neoplastic cells. Abnormalities in the expression and cellular localisation of E-cadherin are frequently associated with high tumor grade, infiltrative growth and lymph node metastasis in a variety of human malignancies. Therefore we screened a panel of different melanoma and colorectal carcinoma cell lines for mutations in all of E-cadherin exons and the corresponding intron-exon junctions. We sequenced the entire 16 exons and flanking intron regions of the E-cadherin gene in all cell lines. In the melanoma cell lines were no mutation detected either in the coding region nor in the flanking intron-extron boundaries. In the colorectal carcinoma cell line HTC 116 we found in exon 3 the deletion of the base 196 (Guanin). It leads to a frame shift mutation. Furthermore we found in all colorectal carcinoma cell lines the mutation of the base 139 in exon 13. This mutation doesn´t change the amino acid sequence, because it still encodes the amino acid Alanin. Three new intronic polymorphisms were detected, none of which affected a region critical for exon-intron processing. Results from our present study suggest that inactivating E-cadherin mutations are not common genetic mechanism in colorectal and melanoma tumorigenesis. The fact that E-cadherin expression and function is often perturbed may be explained by nonmutational mechanisms. In conclusion, our data lend support to the important invasion/tumor-supressor role of E-cadherin and emphasizes the case for further investigation of the role of E-cadherin changes in specific subtipes of tumors. |
