ABCG2/BCRP gene expression is related to epithelial–mesenchymal transition inducer genes in a papillary thyroid carcinoma cell line (TPC-1)
Tumor malignancy is associated with the epithelial–mesenchymal transition (EMT) process and resistance to chemotherapy. However, little is known about the relationship between the EMT and the multidrug-resistance gene in thyroid tumor progression. We investigated whether the expression of theABCG2/BCRPgene is associated withZEB1and other EMT inducer genes involved in tumor dedifferentiation. We established a subpopulation of cells that express theABCG2/BCRPgene derived from the thyroid papillary carcinoma cell line (TPC-1), the so-called TPC-1 MITO-resistant subline. The most relevant findings in these TPC-1 selected cells were a statistically significant upregulation ofZEB1andTWIST1(35- and 15-fold change respectively), no changes in the relative expression of vimentin andSNAIL1, and no expression of E-cadherin. The TPC-1 MITO-resistant subline displayed a faster migration and greater invasive ability than parental cells in correlation with a significant upregulation of the survivin (BIRC5) gene (twofold change,P<0.05). The knockdown ofZEB1promoted nuclear re-expression of E-cadherin, reduced expression of vimentin, N-cadherin, andBIRC5genes, and reduced cell migration (P<0.05). Analysis of human thyroid carcinoma showed a slight overexpression of theABCG2/BCRPat stages I and II (P<0.01), and a higher overexpression at stages III and IV (P<0.01).SNAIL1,TWIST1, andZEB1genes showed higher expression at stages III and IV than at stages I and II. E- and N-cadherin genes were upregulated at stages I and II of the disease (ninefold and tenfold change, respectively,P<0.01) but downregulated at stages III and IV (fourfold lower,P<0.01). These results could be a promising starting point for further study of the role of theABCG2/BCRPgene in the progression of thyroid tumor.