Endocrine Abstracts (2016) 42 P7 | DOI: 10.1530/endoabs.42.P7

μ-Crystalline as hormone antagonist in prostate cancer

Olaf Merkel1,, Osman Aksoy1,, Martin Suzani1,2,3, Melanie Hassler1,4, Karin Schlangen5, Theresa Balber6, Markus Mitterhauser6, Ali Moazzami7, Michaela Schlederer1, Suzanne Turner1,8, Gerda Egger1, Gregor Hörmann9, Markus Hacker6, Zoran Culig10, Jan Pencik1,2 & Lukas Kenner1,2,11

1Department of Clinical Pathology, Medical University Vienna, Vienna, Austria; 2Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria; 3Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria; 4Department of Urology, Medical University of Vienna, Vienna, Austria; 5Department of Biosimulation and Bioinformatics, Medical University Vienna, Vienna, Austria; 6Department of Nuclear Medicine, Medical University Vienna, Vienna, Austria; 7Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, Uppsala, Uppsala, Sweden; 8Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; 9Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria; 10Department of Urology, Medical University Innsbruck, Innsbruck, Austria; 11Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria. These authors contributed equally.

Prostate cancer (PCa) is the most frequent cancer in men in the western world. PCa growth is highly dependent on androgens and androgen ablation is the cornerstone of current therapeutic approaches. μ-Crystalline (CRYM) is the main component of the kangaroohs eye’s lens. CRYM binds thyroid hormone (T3) in a NADPH dependent manner thereby sequestering it from being transcriptionally active in the nucleus. The role of CRYM in prostate cancer is largely unknown. This study identifies low CRYM as a negative prognostic factor in PCa using IHC and Kaplan-Meier analysis. In PCa CRYM expression was reduced, an effect that is further pronounced in metastases. In contrast, thyroid hormone receptor ß (TRβ) showed high expression in PCa that is again increased in metastases. Overexpression of CRYM in PCa cell lines led to increased uptake T3 and reduced invasive capacity. RNA sequencing transcriptome analysis of CRYM overexpressing PCa cell lines reveals androgen receptor and dihydrotestosteron induced genes to be highly specifically suppressed, identifying CRYM as a key hormone antagonist in PCa. Moreover, high CRYM expression leads to deregulated lipid metabolism. Finally, metabolome analysis using nuclear magnetic resonance (NMR) shows that high CRYM expression drastically reduces intracellular choline levels and is able to mask T3 effects in metastatic PC3 PCa cell line. Using PET/MRI we recently described choline levels as non-invasive biomarker for PCa surveillance. This study identifies CRYM as a prognostic factor and key antagonist to T3 and androgen signalling in PCa.

Presenting Author: Olaf Merkel, Department of Clinical Pathology, Medical University Vienna, Währinger Gürtel 18-20, 1090 Wien, Austria. Email: olaf.merkel@meduniwien.ac.at