title: ABCG2/BCRP gene expression is related to epithelial-mesenchymal transition inducer genes in a papillary thyroid carcinoma cell line (TPC-1).
abstract: 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.
authors.affiliation: Thyroid Neoplasia Study Group, EDUAB-HSP, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) Departament de Biologia Cel-lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Spain Departments of Endocrinology and Nutrition General Surgery Pathology IIB, Hospital de la Santa Creu i Sant Pau- Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Mato
authors.forename: C
authors.initials: C
authors.lastname: González
authors.forename: A
authors.initials: A
authors.lastname: Moral
authors.forename: J I
authors.initials: JI
authors.lastname: Pérez
authors.forename: O
authors.initials: O
authors.lastname: Bell
authors.forename: E
authors.initials: E
authors.lastname: Lerma
authors.forename: A
authors.initials: A
authors.lastname: de Leiva
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D000077022:Survivin; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000096:biosynthesis; D015854:Up-Regulation; D014746:Vimentin / Q000096:biosynthesis; D055815:Young Adult; D000071799:Zinc Finger E-box-Binding Homeobox 1; D016335:Zinc Fingers / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C107489:BIRC5 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D000077022:Survivin; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: ABCG2/BCRP gene; EMT inducer genes; papillary thyroid carcinoma cell line (TPC-1)