Overexpression of Nrp/b (nuclear restrict protein in brain) suppresses the malignant phenotype in the C6/ST1 glioma cell line

J Steroid Biochem Mol Biol. 2009 Nov;117(4-5):107-16. doi: 10.1016/j.jsbmb.2009.07.009. Epub 2009 Aug 12.

Abstract

Upon searching for glucocorticoid-regulated cDNA sequences associated with the transformed to normal phenotypic reversion of C6/ST1 rat glioma cells, we identified Nrp/b (nuclear restrict protein in brain) as a novel rat gene. Here we report on the identification and functional characterization of the complete sequence encoding the rat NRP/B protein. The cloned cDNA presented a 1767 nucleotides open-reading frame encoding a 589 amino acids residues sequence containing a BTB/POZ (broad complex Tramtrack bric-a-brac/Pox virus and zinc finger) domain in its N-terminal region and kelch motifs in its C-terminal region. Sequence analysis indicates that the rat Nrp/b displays a high level of identity with the equivalent gene orthologs from other organisms. Among rat tissues, Nrp/b expression is more pronounced in brain tissue. We show that overexpression of the Nrp/b cDNA in C6/ST1 cells suppresses anchorage independence in vitro and tumorigenicity in vivo, altering their malignant nature towards a more benign phenotype. Therefore, Nrp/b may be postulated as a novel tumor suppressor gene, with possible relevance for glioblastoma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cloning, Molecular
  • DNA, Complementary
  • Gene Expression Regulation
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Immunohistochemistry
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics*
  • Molecular Sequence Data
  • Neuropeptides / chemistry
  • Neuropeptides / genetics*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Rats
  • Sequence Homology, Amino Acid

Substances

  • DNA, Complementary
  • Microfilament Proteins
  • Neuropeptides
  • Nuclear Proteins
  • ectodermal-neural cortex 1 protein