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
|