ABCG2/BCRP gene expression is related to epithelial-mesenchymal transition inducer genes in a papillary thyroid carcinoma cell line (TPC-1)
Por:
Mato, E, Gonzalez, C, Moral, A, Perez, JI, Bell, O, Lerma, E, de Leiva, A
Publicada:
1 jun 2014
Resumen:
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.
Filiaciones:
Mato, E:
Univ Barcelona, Biomed Res Networking Ctr Bioengn Biomat & Nanome, EDUAB HSP, Thyroid Neoplasia Study Grp, E-08007 Barcelona, Spain
Univ Barcelona, Fac Med, Dept Biol Cel Lular Immunol & Neurociencies, E-08007 Barcelona, Spain
Gonzalez, C:
Univ Barcelona, Biomed Res Networking Ctr Bioengn Biomat & Nanome, EDUAB HSP, Thyroid Neoplasia Study Grp, E-08007 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Endocrinol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Nutr, E-08193 Barcelona, Spain
Moral, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Perez, JI:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Bell, O:
Univ Barcelona, Biomed Res Networking Ctr Bioengn Biomat & Nanome, EDUAB HSP, Thyroid Neoplasia Study Grp, E-08007 Barcelona, Spain
Lerma, E:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Pathol IIB, E-08193 Barcelona, Spain
de Leiva, A:
Univ Barcelona, Biomed Res Networking Ctr Bioengn Biomat & Nanome, EDUAB HSP, Thyroid Neoplasia Study Grp, E-08007 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Endocrinol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Nutr, E-08193 Barcelona, Spain
Bronze
|