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Endocrine Abstracts (2015) 37 OC8.1 | DOI: 10.1530/endoabs.37.OC8.1

ECE2015 Oral Communications Endocrine tumours (5 abstracts)

A role for vault particles as a marker for therapeutic effects against endocrine tumours

Constanze Hantel & Felix Beuschlein


Endocrine Research Unit, Medizinische Klinik and Poliklinik IV, Ludwig‐Maximilians‐University, Munich, Germany.


The vault complex, consisting of a major vault protein (MVP), two minor vault proteins (VPARP and TEP1) and small untranslated RNA molecules (vault RNAs 1–4), is considered the largest intracellular ribonucleoprotein particle. Although in recent years, vaults were believed to be involved in multidrug resistance, the exact function of this complex has remained unclear. Recently, we investigated the therapeutic applicability of a Tumour-Vascular-Disrupting Agent (ASA) in preclinical models for neuroendocrine tumours of the gastroenteropancreatic system (BON) and adrenocortical carcinoma (NCIh295R). Upon treatment we detected highly significant anti-tumoural effects in BON xenografts which were not evident in NCI-H295R. In an attempt to explain differences in therapeutic responsiveness, gene expression patterns within these tumours were investigated by a gene array. Subsequent analyses identified vault RNAs 1–3 as the most pronounced regulated transcripts in the tumour model showing therapeutic responsiveness. Quantitative real time PCR confirmed these results for ASA treated BON tumours (% of 100% controls; vault1: 2468.1±367%, P<0.001; vault2: 1922.5±235%, P<0.001; vault3: 901.3±119%, P<0.001) while no changes were detectable for the not-responding NCI-H295R-xenografts (% of 100% controls; vault1: 224.1±84%, P>0.05; vault2: 113±23%, P>0.05; vault3: 89±14%, P>0.05). Subsequently, we investigated NCI-H295R-xenografts which had been treated with two different chemotherapeutic regimens (EDP-M and LEDP-M). In this therapeutic setting treatment-dependent upregulation of vault RNAs could also be detected in NCI-H295R-tumors (% of 100% controls; vault1: EDP-M 296.3±44%, P<0.001; LEDP-M 243.5±16%, P<0.001; vault2: EDP-M 157.2±20%, P>0.05; LEDP-M 160.7±20%, P>0.05; vault3: EDP-M 241.2±55%, P<0.001; LEDP-M 118.9±16%, P>0.05). Further in vitro analyses revealed dynamic changes in vault RNA expression also upon blasticidin, doxorubicin, mitotane treatment and a significant increase in MVP protein levels upon TNF alpha treatment in BON cells. In summary, further investigation and modulation of vault particles might have potential to improve efficacy of anticancer drugs in endocrine tumours.

Disclosure: This work was supported by the Wilhelm-Sander-Stiftung (grant number 2011.103.1).

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