In order to detect molecular markers for the epidermal growth factor inhibitor 4-(3-chloro-benzyl)- 6,7-dimethoxy-quinazoline (tyrphostin), we investigated the kinetics of p120-catenin and periplakin in the human bucc...In order to detect molecular markers for the epidermal growth factor inhibitor 4-(3-chloro-benzyl)- 6,7-dimethoxy-quinazoline (tyrphostin), we investigated the kinetics of p120-catenin and periplakin in the human buccal mucosa squamous cancer cell line BICR 10 treated with 3 nM tyrphostin. Growth of BICR 10 cells was inhibited by treatment with tyrphostin. Although changes were not observed in the expression of EGFR and p120-catenin, expression of Akt, Src and periplakin in BICR 10 treated with 3 nM tyrphostin tended to decrease. In addition, phosphorylation of EGFR, Akt and Src was inhibited by treatment with tyrphostin. On immunocytochemical staining, immunoreactions with phosphorylated EGFR, phosphorylated Akt and phosphorylated p120-catenin were weak in BICR 10 treated with tyrphostin. There was a slight immunocy to chemical reaction to periplakin in BICR 10 cells induced by tyrphostin. In conclusion, the decrease in phosphorylation in EGFR and p120-catenin by tyrphostin, following the decrease in Src or Akt phosphorylation, may inhibit expression of several growth factors associated with the proliferation and migration of cancer cells.展开更多
Background The presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus （PNP）. Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody ...Background The presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus （PNP）. Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris （PV）, has been proved pathogenic in PNP. Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNP. Envoplakin （EPL） and periplakin （PPL） are recognized by most PNP sera. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments. Methods We characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients＇ sera and their associated tumors by enzyme-linked immunosorbent assay （ELISA） and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes （HEK）, to evaluate the changes of cell-cell adhesion. Results Autoantibodies against EPL and PPL were detected in most PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sera were capable of dissociating cultured human epidermal keratinocytes. Conclusion Autoantibodies against EPL and PPL may also be pathogenic in PNP.展开更多
文摘In order to detect molecular markers for the epidermal growth factor inhibitor 4-(3-chloro-benzyl)- 6,7-dimethoxy-quinazoline (tyrphostin), we investigated the kinetics of p120-catenin and periplakin in the human buccal mucosa squamous cancer cell line BICR 10 treated with 3 nM tyrphostin. Growth of BICR 10 cells was inhibited by treatment with tyrphostin. Although changes were not observed in the expression of EGFR and p120-catenin, expression of Akt, Src and periplakin in BICR 10 treated with 3 nM tyrphostin tended to decrease. In addition, phosphorylation of EGFR, Akt and Src was inhibited by treatment with tyrphostin. On immunocytochemical staining, immunoreactions with phosphorylated EGFR, phosphorylated Akt and phosphorylated p120-catenin were weak in BICR 10 treated with tyrphostin. There was a slight immunocy to chemical reaction to periplakin in BICR 10 cells induced by tyrphostin. In conclusion, the decrease in phosphorylation in EGFR and p120-catenin by tyrphostin, following the decrease in Src or Akt phosphorylation, may inhibit expression of several growth factors associated with the proliferation and migration of cancer cells.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30671890）.
文摘Background The presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus （PNP）. Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris （PV）, has been proved pathogenic in PNP. Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNP. Envoplakin （EPL） and periplakin （PPL） are recognized by most PNP sera. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments. Methods We characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients＇ sera and their associated tumors by enzyme-linked immunosorbent assay （ELISA） and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes （HEK）, to evaluate the changes of cell-cell adhesion. Results Autoantibodies against EPL and PPL were detected in most PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sera were capable of dissociating cultured human epidermal keratinocytes. Conclusion Autoantibodies against EPL and PPL may also be pathogenic in PNP.
