The proteomic 2D-DIGE approach reveals the protein voltage-dependent anion channel 2 as a potential therapeutic target in epithelial thyroid tumours

•We propose the mitochondrial VACD2 protein as a novel gene for developing therapeutic strategies.•The proteomic 2D-DIGE system is a useful tool to identify new candidate genes.•The 2D-DIGE analysis is a useful tool to compare differentially expressed proteins in epithelial thyroid carcinoma. We inv...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2015-03, Vol.404, p.37-45
Main Authors: Mato, Eugenia, Barceló-Batllori, Sílvia, Orera, Irene, Selva, Laia, Corra, Martina, González, Cintia, Bell, Olga, Lerma, Enrique, Moral, Antonio, Pérez, José Ignacio, de Leiva, Alberto
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
bcl-2 Homologous Antagonist-Killer Protein - genetics
bcl-2 Homologous Antagonist-Killer Protein - metabolism
bcl-2-Associated X Protein - metabolism
Cell Line, Tumor
Epithelial thyroid tumours
Female
Humans
Male
Middle Aged
Neoplasms, Glandular and Epithelial - drug therapy
Neoplasms, Glandular and Epithelial - metabolism
Neoplasms, Glandular and Epithelial - pathology
Niacinamide - analogs & derivatives
Niacinamide - pharmacology
Phenylurea Compounds - pharmacology
Proteomics - methods
Therapeutic target
Thyroid Neoplasms - drug therapy
Thyroid Neoplasms - metabolism
Thyroid Neoplasms - pathology
Two-Dimensional Difference Gel Electrophoresis - methods
Up-Regulation
Voltage-dependent anion channel 2
Voltage-Dependent Anion Channel 2 - genetics
Voltage-Dependent Anion Channel 2 - metabolism
Young Adult
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Summary:•We propose the mitochondrial VACD2 protein as a novel gene for developing therapeutic strategies.•The proteomic 2D-DIGE system is a useful tool to identify new candidate genes.•The 2D-DIGE analysis is a useful tool to compare differentially expressed proteins in epithelial thyroid carcinoma. We investigated the role of VDAC2 in human epithelial thyroid tumours using proteomic 2D-DIGE analysis and qRT-PCR. We found a significant up-regulation of VDAC2 in thyroid tumours and in thyroid tumour cell lines (TPC-1 and CAL-62). We did not detect overexpression of VDAC2 in a normal thyroid cell line (Nthy-ori 3-1). Silico analysis revealed that two proteins, BAK1 and BAX, had a strong relationship with VDAC2. BAK1 gene expression showed down-regulation in thyroid tumours (follicular and papillary tumours) and in TPC-1 and CAL-62 cell lines. Transient knockdown of VDAC2 in TPC-1 and CAL-62 promoted upregulation of the BAK1 gene and protein expression, and increased susceptibility to sorafenib treatment. Overexpression of the BAK1 gene in CAL-62 showed lower sorafenib sensitivity than VDAC2 knockdown cells. We propose the VDAC2 gene as a novel therapeutic target in these tumours.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2015.01.021