Expression and significance of sonic hedgehog signaling pathway-related components in brainstem and supratentorial astrocytomas

Chin Med J (Engl). 2011 Nov;124(21):3515-20.

Abstract

Background: Studies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma.

Methods: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests.

Results: The mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 (PTCH1) was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue (P < 0.01). Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level (P < 0.05).

Conclusions: Enhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma, and could be an ideal therapeutic target in brainstem glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Astrocytoma / genetics
  • Astrocytoma / metabolism*
  • Brain Stem Neoplasms / genetics
  • Brain Stem Neoplasms / metabolism*
  • Female
  • Glioma / genetics
  • Glioma / metabolism*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Patched Receptors
  • Patched-1 Receptor
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Supratentorial Neoplasms / genetics
  • Supratentorial Neoplasms / metabolism*
  • Young Adult

Substances

  • Hedgehog Proteins
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface
  • SHH protein, human