Molecular and Cellular Endocrinology 2015-03-15

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

Eugenia Mato, Sílvia Barceló-Batllori, Irene Orera, Laia Selva, Martina Corra, Cintia González, Olga Bell, Enrique Lerma, Antonio Moral, José Ignacio Pérez, Alberto de Leiva

Index: Mol. Cell. Endocrinol. 404 , 37-45, (2015)

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Abstract

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.