Journal article
Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma
EK Baker, S Taylor, A Gupte, AM Chalk, S Bhattacharya, AC Green, TJ Martin, D Strbenac, MD Robinson, LE Purton, CR Walkley
Bone | Published : 2015
Abstract
Wnt pathway targeting is of high clinical interest for treating bone loss disorders such as osteoporosis. These therapies inhibit the action of negative regulators of osteoblastic Wnt signaling. The report that Wnt inhibitory factor 1 (. WIF1) was epigenetically silenced via promoter DNA methylation in osteosarcoma (OS) raised potential concerns for such treatment approaches. Here we confirm that Wif1 expression is frequently reduced in OS. However, we demonstrate that silencing is not driven by DNA methylation. Treatment of mouse and human OS cells showed that Wif1 expression was robustly induced by HDAC inhibition but not by methylation inhibition. Consistent with HDAC dependent silencing,..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by grants from the Cancer Council of Victoria (to C.W., E.B., M.R.; Grant-In-Aid 1047593); NHMRC Career Development Award (to C.W.; 559016); Cure Cancer Australia Foundation Fellowship (to E.B); 5point foundation (to E.B); NHMRC project grant (to L.P.; 1006485); NHMRC Senior Research Fellowship (to L.P.; 1003339); in part by the Victorian State Government Operational Infrastructure Support Program (to St. Vincent's Institute). C.W. is the Philip Desbrow Senior Research Fellow of the Leukaemia Foundation. We thank the SVI Flow Cytometry Core Facility (M Thomson, E Orlowski) for FACS sorting and advice.