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

Mol Cell Endocrinol. 2015 Mar 15:404:37-45. doi: 10.1016/j.mce.2015.01.021. Epub 2015 Jan 21.

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.

Keywords: Epithelial thyroid tumours; Therapeutic target; Voltage-dependent anion channel 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • 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*
  • Sorafenib
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Two-Dimensional Difference Gel Electrophoresis / methods*
  • Up-Regulation
  • Voltage-Dependent Anion Channel 2 / genetics
  • Voltage-Dependent Anion Channel 2 / metabolism*
  • Young Adult
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAK1 protein, human
  • BAX protein, human
  • Phenylurea Compounds
  • VDAC2 protein, human
  • Voltage-Dependent Anion Channel 2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Niacinamide
  • Sorafenib