engleski

Beta-catenin expression is upregulated in cisplatin resistant human carcinoma cell lines

Acquired resistance to cisplatin represents a major obstacle to successful chemotherapy. Since cisplatin resistant CA3ST and CK2 cells exhibited altered formation of cell-cell adhesions, comparing to their parental human laryngeal carcinoma HEp-2 cell line, we analyzed the expression of proteins involved in the formation of these structures in this model of cisplatin resistance. While there was no change in the expression of N-cadherin, desmoglein and p120 catenin, plakoglobin expression was strongly downregulated and beta-catenin expression upregulated in both cisplatin resistant variants. Immunocytochemistry revealed membranous localization of both catenins. Although CA3ST and CK2 cells displayed decreased plakoglobin mRNA, they had similar expression of beta-catenin mRNA as HEp-2 cells. Immunoprecipitation of cadherin-catenin complexes revealed lower incidence of plakoglobin and higher incidence of beta-catenin in the complex with N-cadherin in both CA3ST and CK2 cells, which implies that increased expression of beta-catenin results from its stabilization through interaction with N-cadherin. While single cisplatin treatment of HEp-2 cells induced proteolytic cleavage of both plakoglobin and beta-catenin, it had no influence on their mRNA levels, suggesting that the difference in catenin ratio is a slowly-generating process which requires repeated cisplatin exposure. Since vincristine resistant cells did not upregulate beta-catenin, while another cisplatin resistant cell line also showed beta-catenin upregulation, we speculate this could be a general phenomena accompanying cisplatin resistance.

cisplatin; drug-resistance; beta-catenin; plakoglobin; cell adhesion

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