FK506 binding protein mediates glioma cell growth and sensitivity to rapamycin treatment by regulating NF-kappaB signaling pathway. Academic Article uri icon

Overview

abstract

  • FK506 binding protein 5 (FKBP5) belongs to a family of immunophilins named for their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis-trans isomerases, and also with chaperones to help protein folding. Using glioma cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were then examined. We found that cell growth was suppressed after FKBP5 expression was inhibited by short interfering RNA transfection and enhanced by FKBP5 overexpression. Electrophoretic mobility shift assay showed that nuclear factor-kappa B (NF-kappaB) and DNA binding was enhanced by FKBP5 overexpression. The expression level of I-kappa B alpha and phosphorylated NF-kappaB was regulated by the expression of FKBP5. These data suggest that FKBP5 is involved in NF-kappaB pathway activation in glioma cells. In addition, FKBP5 overexpression in rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment, whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting that the FKBP5 regulates glioma cell response to rapamycin treatment. In conclusion, our study demonstrates that FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-kappaB pathway.

publication date

  • March 1, 2008

Research

keywords

  • Antibiotics, Antineoplastic
  • Brain Neoplasms
  • Drug Resistance, Neoplasm
  • Glioma
  • NF-kappa B
  • Sirolimus
  • Tacrolimus Binding Proteins

Identity

PubMed Central ID

  • PMC2259453

Scopus Document Identifier

  • 40349098670

Digital Object Identifier (DOI)

  • 10.1593/neo.07929

PubMed ID

  • 18320068

Additional Document Info

volume

  • 10

issue

  • 3