Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer.

Autor: Aksoy O; Department of Pathology, Medical University Vienna, Vienna, Austria., Pencik J; Department of Pathology, Medical University Vienna, Vienna, Austria.; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.; Present address: Jan Pencik, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA., Hartenbach M; Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Vienna, Austria., Moazzami AA; Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden., Schlederer M; Department of Pathology, Medical University Vienna, Vienna, Austria., Balber T; Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Vienna, Austria.; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria.; Department for Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria., Varady A; Department of Pathology, Medical University Vienna, Vienna, Austria., Philippe C; Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Vienna, Austria., Baltzer PA; Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Vienna, Austria., Mazumder B; School of Pharmacy, University of Nottingham, Nottingham, UK., Whitchurch JB; School of Pharmacy, University of Nottingham, Nottingham, UK., Roberts CJ; School of Pharmacy, University of Nottingham, Nottingham, UK., Haitel A; Department of Pathology, Medical University Vienna, Vienna, Austria., Herac M; Department of Pathology, Medical University Vienna, Vienna, Austria., Susani M; Department of Pathology, Medical University Vienna, Vienna, Austria., Mitterhauser M; Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Vienna, Austria.; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria., Marculescu R; Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria., Stangl-Kremser J; Department of Urology, Medical University Vienna, Vienna, Austria., Hassler MR; Department of Urology, Medical University Vienna, Vienna, Austria., Kramer G; Department of Urology, Medical University Vienna, Vienna, Austria., Shariat SF; Department of Urology, Medical University Vienna, Vienna, Austria.; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan.; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.; Departments of Urology, Weill Cornell Medical College, New York, New York, USA.; Department of Urology, University of Texas Southwestern, Dallas, Texas, USA.; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic., Turner SD; Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK.; Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Tichy B; Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Oppelt J; Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Pospisilova S; Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic., Hartenbach S; Histo Consulting Inc., Ulm, Germany.; Department of Pathology, Rudolfinerhaus Privatklinik Gmbh, Vienna, Austria., Tangermann S; Unit for Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria., Egger G; Department of Pathology, Medical University Vienna, Vienna, Austria.; Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria., Neubauer HA; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria., Moriggl R; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria., Culig Z; Department of Urology, Innsbruck Medical University, Innsbruck, Austria., Greiner G; Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria., Hoermann G; Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria.; MLL Munich Leukemia Laboratory, Munich, Germany., Hacker M; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.; Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Vienna, Austria., Heery DM; School of Pharmacy, University of Nottingham, Nottingham, UK., Merkel O; Department of Pathology, Medical University Vienna, Vienna, Austria., Kenner L; Department of Pathology, Medical University Vienna, Vienna, Austria.; Center for Biomarker Research in Medicine (CBmed), Graz, Austria.; Unit for Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria.; Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2021 Feb 01; Vol. 148 (3), pp. 731-747. Date of Electronic Publication: 2020 Oct 31.
DOI: 10.1002/ijc.33332
Abstrakt: Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.
(© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)
Databáze: MEDLINE
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