Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors

J Clin Neurosci. 2010 Dec;17(12):1515-9. doi: 10.1016/j.jocn.2010.03.051. Epub 2010 Sep 21.

Abstract

The aim of this study was to investigate the expression of microtubule-associated protein 1 light chain 3B (LC3B) and the autophagy-related gene Beclin 1 in astrocytic tumors and to analyze their expression profiles with respect to the development of astrocytic tumors. The expression patterns of LC3B and Beclin 1 were analyzed by immunohistochemistry and/or western blotting in tumor samples from 62 patients with different grades of astrocytic tumor. The expression patterns of LC3B and Beclin 1 were correlated with the pathological and clinical characteristics of the patients. Western blot analysis indicated that the average optical densitometry (OD) ratio of Beclin 1 in high-grade astrocytic tumors (World Health Organization [WHO] grade III/IV) was lower than in low-grade astrocytic tumors (WHO grade I/II, p = 0.036). The expression of LC3B-I exhibited no significant difference among the various grades of astrocytic tumor. However, the average OD ratio of LC3B-II was lower in glioblastoma multiforme (GBM) than in other grades of astrocytic tumor (p = 0.030). The expression levels of Beclin 1 and LC3B-II were related to survival time and they were also correlated with each other (p = 0.035). In addition, down-regulation of LC3B-II and Beclin 1 expression was associated with GBM. The progression of astrocytic tumors was related to a decrease in autophagic capacity represented by the loss of LC3B-II and Beclin 1 expression.

MeSH terms

  • Adult
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Autophagy
  • Beclin-1
  • Blotting, Western
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / biosynthesis*
  • Microtubule-Associated Proteins / biosynthesis*
  • Middle Aged

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins