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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2021

AutorInnen: Aksoy, O; Pencik, J; Hartenbach, M; Moazzami, AA; Schlederer, M; Balber, T; Varady, A; Philippe, C; Baltzer, PA; Mazumder, B; Whitchurch, JB; Roberts, CJ; Haitel, A; Herac, M; Susani, M; Mitterhauser, M; Marculescu, R; Stangl-Kremser, J; Hassler, MR; Kramer, G; Shariat, SF; Turner, SD; Tichy, B; Oppelt, J; Pospisilova, S; Hartenbach, S; Tangermann, S; Egger, G; Neubauer, HA; Moriggl, R; Culig, Z; Greiner, G; Hoermann, G; Hacker, M; Heery, DM; Merkel, O; Kenner, L

Titel: Thyroid and androgen receptor signaling are antagonized by CRYM in prostate cancer.

Quelle: Int J Cancer. 2021 148 (3) 731-747.



Autor/innen der Vetmeduni Vienna:

Kenner Lukas
Moriggl Richard
Neubauer Heidi
Tangermann Simone

Beteiligte Vetmed-Organisationseinheiten
Institut für Tierzucht und Genetik, Abteilung für Funktionelle Krebsgenomik
Institut für Pathologie, Abteilung für Labortierpathologie


Abstract:
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.

Keywords Pubmed: Cell Line, Tumor
Cholineadministration & dosageanalogs & derivatives
Cohort Studies
Crystallinsgeneticsmetabolism
Down-Regulation
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Metabolomics
Neoplasm Staging
PC-3 Cells
Positron Emission Tomography Computed Tomography
Prognosis
Prostatic Neoplasmsdiagnostic imaginggeneticsmetabolismpathology
Receptors, Androgengeneticsmetabolism
Receptors, Thyroid Hormonegenetics
Sequence Analysis, RNA
Signal Transduction
Tissue Array Analysis
Triiodothyronineantagonists & inhibitorsmetabolism

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