Androgens2016 Poster Presentations (1) (42 abstracts)
High levels of the AR-V7 splice variant and co-amplification of the Golgi protein coding YIPF6 in AR amplified prostate cancer bone metastases
Erik Djusberg 1* , Emma Jernberg 1* , Elin Thysell 1 , Irina Golovleva 2 , Pia Lundberg 2 , Sead Crnalic 3 , Anders Widmark 4 , Anders Bergh 1 , Maria Brattsand 1 & Pernilla Wikström 1
1Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden; 2Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden; 3Department of Perioperative Sciences, Orthopedics, Umeå University, Umeå, Sweden; 4Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden *Contributed equally
The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistance in prostate cancer, such as increased expression of constitutively active AR variants and steroid-converting enzymes have been poorly examined. Specific aims of this study were to examine AR amplification in treatment-naïve and castration-resistant prostate cancer (CRPC) bone metastases and to explore molecular and functional differences. AR gene amplification was assessed and verified in 16 (53%) of the CRPC bone metastases (n=30), and in none of the untreated bone metastases (n=10). AR gene amplification was associated with increased AR mRNA levels and its constitutively active AR-V7 splice variant, as well as with co-amplification of genes in the AR proximity at Xq12, such as YIPF6. Therefore, the paper focused on evaluating functional effects of YIPF6 overexpression. Members of the Yip1 protein family are mainly localized to the ER and Golgi apparatus and are thought to be involved in vesicle transport. Here we demonstrate YIPF6 protein expression in the Golgi of PC cells, and show that overexpression leads to reduced cell proliferation and colony formation. Interestingly, high YIPF6 levels also increased production of extracellular vesicles (EVs) containing coagulation factors such as tissue factor, fibrinogen and factor XIII. While investigating the EVs in vitro an ability to stimulate blood coagulation was demonstrated, and we therefore suggest that YIPF6 amplification and overexpression in CRPC bone tumors may lead to a local and systemic stimulation of coagulation mediated by pro-coagulant EVs.
Funding: Swedish Research Council, Swedish Cancer Society, Cancer Research Foundation in Northern Sweden, Lion’s Cancer Research Foundation, The county of Västerbotten, and Umeå University.
Presenting Author: Erik Djusberg, Umeå universitet, Institutionen för medicinsk biovetenskap, Umeå Sweden. Email: [email protected]
Volume 42
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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