Journal article

Targeting XIAP and PPAR gamma in Granulosa Cell Tumors Alters Metabolic Signaling

Dilys TH Leung, Adam Rainczuk, Nguyen Trang, Andrew Stephens, John Silke, Peter J Fuller, Simon Chu

JOURNAL OF PROTEOME RESEARCH | AMER CHEMICAL SOC | Published : 2019

Abstract

Ovarian granulosa cell tumors (GCTs) are hormonally active cancers characterized by indolent growth and late, invasive relapse. No therapies have yet proven to be efficacious. We previously reported that the inhibition of the antiapoptotic X-linked inhibitor of apoptosis protein (XIAP) removes transrepression of the pro-proliferative nuclear receptor, peroxisome proliferator-activated receptor (PPAR)-γ, in a GCT-derived cell line, KGN. Both PPARγ and XIAP are overexpressed in human GCT. The inhibition of XIAP with the restoration of PPARγ signaling using a SMAC-mimetic (Compound A (CmpdA)) and rosiglitazone (RGZ)/retinoic acid (RA), respectively, reduced cell proliferation and induced apopto..

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University of Melbourne Researchers

Grants

Awarded by National Health & Medical Research Council of Australia


Awarded by DoD CDMRP


Funding Acknowledgements

We acknowledge Dr. Peter Hoffmann and Dr. Georgia Arentz at Adelaide Proteomics Centre for mass spectrometry analysis of the samples, Maria Alexiadis for the microarray data, and the MHTP Medical Genomics Facility, Melbourne, Australia as the service provider for quantitative PCR. This work was supported by grants-in-aid from the Cancer Council Victoria; the Ovarian Cancer Research Foundation and the Rivkin Centre (SC); the Granulosa Cell Tumor of the Ovary Foundation; the National Health & Medical Research Council of Australia through a project grant (grant number 1058334); the DoD CDMRP, grant number W81XWH-17-0CRP-IIRA-cfda12.420; and an Endocrine Society of Australia Research Higher Degree Scholarship to D.T.H.L. We would like to acknowledge the MHTP medical Genomics Facility, Melbourne, Australia, as the service provider for quantitative Digital PCR Fluidigm Analysis. The Hudson Institute and the Walter and Eliza Hall Institute are supported by the Victorian Government's Operational Infrastructure Scheme.