Axin induces cell death and reduces cell proliferation in astrocytoma by activating the p53 pathway

Int J Oncol. 2009 Jul;35(1):25-32. doi: 10.3892/ijo_00000309.

Abstract

Astrocytic tumors are the most common brain tumors with various genetic defects. As a tumor suppressor gene, Axin could control cell death and growth. Axin possesses a separate domain that directly interacts with p53 and regulates the activity of p53 pathway. Our aims were to elucidate the effects of Axin on the progression of astrocytoma. We examined the expression of Axin in 96 cases of astrocytoma using immunohistochemistry. The apoptotic index, proliferactive acitivity and the expression levels of p53 and its downstream genes, p21 and Cyclin D1, were evaluated in the C6 astrocytoma cells with overexpression or silencing of Axin. The results showed the levels of Axin correlated significantly inversely with the grades of astrocytoma (R=-0.286, P<0.05) and correlated negatively with Ki-67 labeling index (R=-0.227, P<0.05). Overexpression of Axin in C6 cells induces cell death, and reduces the cell proliferation, up-regulates the expression of p53. Silencing of Axin reduces p53 expression. The p53 inhibitor, pifithrin-alpha, was able to counteract the effect of Axin in C6 cells. Our data demonstrate that the expression of Axin is associated negatively with the progression of astrocytoma. In conclusion, Axin induces cell death and reduces cell proliferation, partially by activating the p53 pathway in astrocytoma cells. This knowledge is helpful in understanding the role of Axin in the progression of astrocytoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Apoptosis* / drug effects
  • Astrocytoma / genetics
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Axin Protein
  • Benzothiazoles / pharmacology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Child
  • Child, Preschool
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • RNA Interference
  • Rats
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Toluene / analogs & derivatives
  • Toluene / pharmacology
  • Transfection
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / metabolism*
  • Young Adult

Substances

  • Axin Protein
  • Benzothiazoles
  • Ccnd1 protein, rat
  • Cdkn1a protein, rat
  • Cyclin-Dependent Kinase Inhibitor p21
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Toluene
  • pifithrin