Nucleophosmin delocalization in thyroid tumour cells

Endocr Pathol. 2011 Mar;22(1):18-23. doi: 10.1007/s12022-011-9147-x.

Abstract

Nucleophosmin (NPM) is a multifunctional nucleolar protein that, depending on the context, can act as oncogene or tumour suppressor. Mutations of the NPM1 gene induce delocalization of NPM in acute myeloid leukaemia. Differently, in solid tumours, only NPM overexpression, but not delocalization, has been so far reported. Here, NPM localization in thyroid tumours was investigated. By using immunohistochemistry, we show increase of NPM cytoplasmic localization in follicular adenomas and papillary carcinomas compared to normal thyroid tissue (p = 0.0125 and <0.0001, respectively). NPM1 mutations commonly found in human leukaemia are not present in thyroid tumours. Immunofluorescence in cultured cell lines was utilized to discriminate between nucleolar and nuclear localization. We show that in thyroid cancer cell lines NPM localizes both in the nucleolus and in nucleus, while in non-tumorigenic thyroid cell lines localizes only in nucleolus. Either presence of the histone deacetylase inhibitor trichostatin A or absence of thyroid-stimulating hormone induces NPM nuclear localization in non-tumorigenic thyroid cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / drug therapy
  • Adenocarcinoma, Follicular / metabolism*
  • Adenocarcinoma, Follicular / pathology
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Biomarkers, Tumor / metabolism
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma, Papillary / drug therapy
  • Carcinoma, Papillary / metabolism*
  • Carcinoma, Papillary / pathology
  • Cell Line, Tumor
  • Cell Nucleolus / metabolism
  • Cell Nucleolus / pathology
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis
  • Humans
  • Hydroxamic Acids / pharmacology
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Thyrotropin / deficiency
  • Thyrotropin / pharmacology

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Hydroxamic Acids
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • trichostatin A
  • Thyrotropin