Related to testes-specific, vespid, and pathogenesis protein-1 (RTVP-1) is overexpressed in gliomas and regulates the growth, survival, and invasion of glioma cells

Cancer Res. 2006 Apr 15;66(8):4139-48. doi: 10.1158/0008-5472.CAN-05-2851.

Abstract

In this study, we examined the expression and functions of related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was expressed in high levels in glioblastomas, whereas its expression in low-grade astrocytomas and normal brains was very low. Transfection of glioma cells with small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the cell lines examined and induced cell apoptosis in some of them. Overexpression of RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage-independent growth of the cells. In addition, overexpression of RTVP-1 rendered glioma cells more resistant to the apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand and serum deprivation. To delineate the molecular mechanisms involved in the survival effects of RTVP-1, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase and increased the expression of Bcl2 and that the protective effect of RTVP-1 was partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion of glioma cells as was evident by their enhanced migration through Matrigel and by their increased invasion in a spheroid confrontation assay. The increased invasive potential of the RTVP-1 overexpressors was also shown by the increased activity of matrix metalloproteinase 2 in these cells. Our results suggest that the expression of RTVP-1 is correlated with the degree of malignancy of astrocytic tumors and that RTVP-1 is involved in the regulation of the growth, survival, and invasion of glioma cells. Collectively, these findings suggest that RTVP-1 is a potential therapeutic target in gliomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / physiology
  • Astrocytoma / enzymology
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Glioblastoma / enzymology
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioma / enzymology
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Membrane Proteins
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Nerve Tissue Proteins / biosynthesis*

Substances

  • GLIPR1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Matrix Metalloproteinase 2