Journal article
Combined PPARg activation and XIAP inhibition as a potential therapeutic strategy for ovarian granulosa cell tumors
DTH Leung, T Nguyen, EM Oliver, J Matti, M Alexiadis, J Silke, TW Jobling, PJ Fuller, S Chu
Molecular Cancer Therapeutics | AMER ASSOC CANCER RESEARCH | Published : 2019
Abstract
Ovarian granulosa cell tumors (GCT) are characterized by indolent growth and late relapse. No therapeutic modalities aside from surgery have proven effective. We previously reported overexpression of the nuclear receptor, peroxisome proliferator-activated receptor-gamma (PPARg), and constitutive activity of the NFkB and AP1 signaling pathways in GCT. PPARg presents as a potential therapeutic target as it impedes proliferation and promotes terminal differentiation of granulosa cells. However, resistance to the actions of PPARg is caused by NFkB transrepression in GCT-derived cell lines, KGN and COV434. We showed that abrogation of NFkB signaling in GCT cells enables PPARg agonists to initiate..
View full abstractGrants
Awarded by Rivkin Center for Ovarian Cancer
Funding Acknowledgements
This work was supported by grants-in-aid from the Cancer Council Victoria (to P.J. Fuller and S. Chu), the Ovarian Cancer Research Foundation (to S. Chu), the Granulosa Cell Tumour of the Ovary Foundation (to S. Chu and P.J. Fuller), the Marsha Rivkin Center for Ovarian Cancer Research (to S. Chu and P.J. Fuller), the National Health & Medical Research Council of Australia through a Project Grant (#1058334; to P.J. Fuller and S. Chu), Ian Potter Foundation for the Seahorse Extracellular Flux XFp Analyzer (to S. Chu), and Endocrine Society of Australia through a Research Higher Degree Scholarship (to D.T.H. Leung). The Hudson Institute is supported by the Victorian Government's Operational Infrastructure Scheme. The authors thank Calvin Chee (Hudson Institute of Medical Research), Nicholas Chee (Hudson Institute of Medical Research), Daniel Heathcote (Hudson Institute of Medical Research), and the MHTP Research Platforms for technical support. We would also like to thank Professor Akira Iwase (Nagoya University Graduate School of Medicine) for kindly providing the hGrC1 cell line (18). We would like to acknowledge MHTP medical Genomics Facility, Melbourne, Australia, as the service provider for quantitative PCR and high content screening.