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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
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,Krdoi
10.1002/ijc.33332subject
Has Abstractpub_date
2021-02-01 00:00:00pages
731-747issue
3eissn
0020-7136issn
1097-0215journal_volume
148pub_type
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