High expression of Aurora-B/Aurora and Ipll-like midbody-associated protein (AIM-1) in astrocytomas

J Neurooncol. Mar-Apr 2004;67(1-2):53-64. doi: 10.1023/b:neon.0000021784.33421.05.

Abstract

Objective: Impaired regulation of Aurora-B/AIM-1 expression in human cells causes chromosomal abnormality and instability, and recent observations of high expression but not mutation of Aurora-B/AIM-1 in human cancers imply that Aurora-B/AIM-1 might be a candidate molecule for cancer progression. We analyzed the effects of modification of Aurora-B/AIM-1 expression on the growth of a human glioma cell line and the expression of Aurora-B/AIM-1 in astrocytomas.

Methods: A glioma cell line, U251MG was transfected with wild type (WT) of Aurora-B/AIM-1 or kinase-inactive mutant of Aurora-B/AIM-1 in order to test the effects of overexpression of WT or kinase-inactive Aurora-B/AIM-1 on cell morphology and cell growth. Brain tissue samples were obtained during surgery and processed for reverse transcription-polymerase chain reaction, immunofluorescence in order to analyze the expression of Aurora-B/AIM-1 mRNA and protein.

Results: Exogenous overexpression of WT of Aurora-B/AIM-1 in cultured cells of U251MG produced multinuclearity and increased ploidy, and inhibited the growth of tumor cells. Exogenous overexpression of kinase-inactive Aurora-B/AIM-1 in a human glioma cell line also suppressed the tumor cell growth without affecting ploidy. Aurora-B/AIM-1 was highly expressed in astrocytomas and U251MG, and mRNA and protein levels of Aurora-B/AIM-1 in tumor tissues well correlated with their histological malignancy (World Health Organization grading). Survival time also negatively correlated with the levels of Aurora-B/AIM-1 mRNA in tumor samples.

Conclusion: Aurora-B/AIM-1 was highly expressed in high-grade gliomas and its expression was well correlated with histological malignancy and clinical outcomes. The modification of the level of Aurora-B/AIM-1 expression might be a new target for glioma therapy.

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / metabolism*
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • Aurora Kinase B
  • Aurora Kinases
  • Biomarkers, Tumor*
  • Blotting, Western
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Crystallins
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins
  • Membrane Transport Proteins / biosynthesis*
  • Middle Aged
  • Prognosis
  • Protein-Serine-Threonine Kinases / biosynthesis*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • AIM1 protein, human
  • Biomarkers, Tumor
  • Crystallins
  • Membrane Proteins
  • Membrane Transport Proteins
  • RNA, Messenger
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases