Abstract:
:The homeobox transcription factor OTX2 plays an essential role during embryonic brain development. It is normally silenced in the adult brain, but is overexpressed by genomic amplification or other mechanisms in the majority of medulloblastomas (MBs). Retinoic acids (RAs) can suppress OTX2 expression and inhibit MB growth. In this study, 9-cis RA most potently inhibited MB cell growth. 9-cis RA functions through the downregulation of OTX2 expression, which subsequently induces neuronal differentiation of OTX2-expressing cells. Treatment with 9-cis RA reduced the growth of D425 flank xenograft tumors in mice. In an intracranial model, however, MB tumors showed resistance to 9-cis RA treatment, and we implicated fibroblast growth factor (FGF) as a potential mediator of resistance to RA therapy. These findings suggest a mechanism for RA-mediated anti-tumor effect on OTX2-positive MB cells and indicate that therapeutic targeting of OTX2 might be effective if FGF pathway-mediated resistance can be overcome.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Bai R,Siu IM,Tyler BM,Staedtke V,Gallia GL,Riggins GJdoi
10.1093/neuonc/nop062subject
Has Abstractpub_date
2010-07-01 00:00:00pages
655-63issue
7eissn
1522-8517issn
1523-5866pii
nop062journal_volume
12pub_type
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