Elevated expression of Notch-1 and EGFR induced apoptosis in glioblastoma multiforme patients

Clin Neurol Neurosurg. 2015 Apr:131:54-8. doi: 10.1016/j.clineuro.2015.01.018. Epub 2015 Jan 28.

Abstract

Objective: The Notch signaling pathway has been well recognized as important adjuster in glioma tumorigenesis and could regulate the glioma cell proliferation through downstream factors such as epidermal growth factor receptor (EGFR). Our current study was aim to investigate the clinical association between Notch-1 gene and EGFR gene as well as cell survival rate in human glioblastoma multiforme (GBM) samples.

Patients and methods: Samples from 90 patients with GBMs and 20 normal brain tissues were analyzed in our study. Western blot and immunohistochemistry was used to detect Notch and EGFR protein expression. RT-PCR was used to detect Notch and EGFR mRNA expression. Apoptosis was detected with flow cytometry.

Results: Results demonstrated that the Notch and EGFR gene mRNA and protein levels were dramatically higher in GBM tissues compared to normal brain. Further analysis found these increased mRNA levels were only associated with patient survival period, but not related to patient age, gender and tumor size. A positive correlation was observed between Notch and EGFR protein expression. The positive correlations were also exhibited between Notch-1, EGFR gene expression and apoptosis percentage.

Conclusion: Our study verified both Notch-1 and EGFR involved in GBM tumorigenesis and may provide important information for GBM clinical treatment and prognosis.

Keywords: Apoptosis; EGFR; Glioblastoma multiforme; Notch-1.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics*
  • Brain Neoplasms / metabolism*
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glioblastoma / metabolism*
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism*
  • Receptor, Notch1 / metabolism*

Substances

  • NOTCH1 protein, human
  • RNA, Messenger
  • Receptor, Notch1
  • EGFR protein, human
  • ErbB Receptors