ABCG2/BCRP gene expression is related to epithelial–mesenchymal transition inducer genes in a papillary thyroid carcinoma cell line (TPC-1)

    1. A de Leiva1,3
    1. 1Thyroid Neoplasia Study Group, EDUAB‐HSP, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN)
      2Departament de Biologia Cel‐lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Spain
      3Departments of Endocrinology and Nutrition
      4General Surgery
      5Pathology IIB, Hospital de la Santa Creu i Sant Pau‐ Universitat Autònoma de Barcelona, Barcelona, Spain
    1. Correspondence should be addressed to E Mato; Email: emato{at}


    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 the ABCG2/BCRP gene is associated with ZEB1 and other EMT inducer genes involved in tumor dedifferentiation. We established a subpopulation of cells that express the ABCG2/BCRP gene 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 of ZEB1 and TWIST1 (35- and 15-fold change respectively), no changes in the relative expression of vimentin and SNAIL1, 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 of ZEB1 promoted nuclear re-expression of E-cadherin, reduced expression of vimentin, N-cadherin, and BIRC5 genes, and reduced cell migration (P<0.05). Analysis of human thyroid carcinoma showed a slight overexpression of the ABCG2/BCRP at stages I and II (P<0.01), and a higher overexpression at stages III and IV (P<0.01). SNAIL1, TWIST1, and ZEB1 genes 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 the ABCG2/BCRP gene in the progression of thyroid tumor.

    • Revision received 4 March 2014
    • Accepted 10 March 2014
    • Made available online as an Accepted Preprint 18 March 2014
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