Etiology and Pathogenesis Molecular Oncology


J Neurooncol. 2004 Mar-Apr;67(1-2):53-64. (Laboratory Investigation)


Abstract

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

Kasumi Araki, Kazuhiko Nozaki, Tetsuya Ueba, Masaaki Tatsuka and Nobuo Hashimoto

Department of Neurosurgery (K.A., K.N., T.U., N.H.), Kyoto University Graduate School of Medicine, Kyoto; Department of Molecular Radiobiology (M.T.), Research Institution for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

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.

PMID: 15072448 [PubMed - indexed for MEDLINE]

Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15072448


 

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