Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours

Int J Oncol. 2007 Feb;30(2):429-36.

Abstract

Beclin 1 is is an autophagy gene, the role of which as a tumour suppressor has recently been recognized in a few studies. We examined the expression of Beclin 1 protein in 212 primary human brain tumours, including 97 high-grade glial tumours, 29 low-grade glial tumours, 4 grade III meningiomas, 19 grade II meningiomas, 52 grade I meningiomas, and 11 medulloblastomas. In 94 cases, including 56 glial tumours, 35 meningiomas, and 3 medulloblastomas we also assessed Beclin 1 mRNA expression by real-time RT-PCR. In most high-grade astrocytic, ependymal neoplasms and atypical meningiomas we found a decrease of cytoplasmic protein expression that was, instead, high in the majority of low-grade tumours and in medulloblastomas. The expression level of Beclin 1 mRNA was significantly lower in glioblastomas than in grade II (p=0.04) and grade I (p=0.01) astrocytomas; in grade III than in grade I astrocytomas (p=0.01); in grade II than in grade I meningiomas (p=0.03); and in all glial tumours when compared to all meningiomas (p<0.0001). Cytoplasmic expression is thought to be linked to the functional protein. Our observations are in line with studies that demonstrated decreased expression of Beclin 1 in human breast, ovarian, prostate and ovarian cancer and furtherly support its involvement also in brain tumours, which had previously been demonstrated in a few experimental studies, both in spontaneous and in therapy-induced autophagy. Furthermore, our study suggests possible differences of Beclin 1 involvement and its role among the different histotypes of brain neoplasms. Further studies are needed to highlight Beclin 1 function in tumour suppression and/or in tumour survival through autophagy and other related programmed cell death processes in brain tumours.

MeSH terms

  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis Regulatory Proteins / physiology
  • Autophagy
  • Beclin-1
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Medulloblastoma / metabolism*
  • Medulloblastoma / pathology
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / physiology
  • Meningioma / metabolism*
  • Meningioma / pathology
  • Oligodendroglioma / metabolism*
  • Oligodendroglioma / pathology
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • RNA, Messenger