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Identification of OTX2 as a Medulloblastoma Oncogene
Whose Product can be Targeted by All-Trans Retinoic Acid
Di C, Liao S, Adamson DC, Parrett TJ, Broderick DK, Shi Q, Lengauer C,
Cummins JM, Velculescu VE, Fults DW, McLendon RE, Bigner DD, Yan H
Brain Tumor Center, Department of Pathology, Duke University Medical Center,
Durham, North Carolina.
Through digital karyotyping of permanent medulloblastoma cell lines, we
found that the homeobox gene OTX2 was amplified more than 10-fold in three
cell lines.
Gene expression analyses showed that OTX2 transcripts were
present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic
histopathologic features.
Knockdown of OTX2 expression by siRNAs inhibited
medulloblastoma cell growth in vitro, whereas pharmacologic doses of
all-trans retinoic acid repressed OTX2 expression and induced apoptosis only
in medulloblastoma cell lines that expressed OTX2.
These observations
suggest that OTX2 is essential for the pathogenesis of anaplastic
medulloblastomas and that these tumors may be amenable to therapy with
all-trans-retinoic acid.
PMID: 15705891 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15705891
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