NOL7 is a nucleolar candidate tumor suppressor gene in cervical cancer that modulates the angiogenic phenotype

Oncogene. 2006 Jan 26;25(4):588-98. doi: 10.1038/sj.onc.1209070.

Abstract

Cervical cancer is associated with human papilloma virus infection. However, this infection is insufficient to induce transformation and progression. Loss of heterozygosity analyses suggest the presence of a tumor suppressor gene (TSG) on chromosome 6p21.3-p25. Here we report the cloning NOL7, its mapping to chromosome band 6p23, and localization of the protein to the nucleolus. Fluorescence in situ hybridization analysis demonstrated an allelic loss of an NOL7 in cultured tumor cells and human tumor samples. Transfection of NOL7 into cervical carcinoma cells inhibited their growth in mouse xenografts, confirming its in vivo tumor suppressor activity. The induction of tumor dormancy correlated with an angiogenic switch caused by a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis inhibitor thrombospondin-1. These data suggest that NOL7 may function as a TSG in part by modulating the expression of the angiogenic phenotype.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Nucleolus / chemistry*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Mice
  • Neovascularization, Pathologic / prevention & control*
  • Thrombospondin 1 / genetics
  • Uterine Cervical Neoplasms / blood supply
  • Uterine Cervical Neoplasms / genetics*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Thrombospondin 1
  • Vascular Endothelial Growth Factor A