ClC-channels and etoposide resistance in the Neuorendocrine Tumour Cell Line LCC-18 [Elektronische Ressource] / von Felix Ernst Rietmann

Aus der Medizinischen Klinik mit Schwerpunkt Hepatologie und Gastroenterologie der Medizinischen Fakultät Charité – Universitätsmedizin Berlin DISSERTATION ClC-channels and Etoposide Resistance in the Neuroendocrine Tumour Cell Line LCC-18 zur Erlangung des akademischen Grades Doctor medicinae (Dr. med.) vorgelegt der Medizinischen Fakultät Charité – Universitätsmedizin Berlin von Felix Ernst Rietmann aus Essen Gutachter: 1. Priv.-Doz. Dr. med. K. Weylandt 2. Prof. Dr. Ch. J. Strasburger 3. Prof. Dr. med. H. Scherübl Datum der Promotion: 19.11.2010 CONTENTS Contents 1 INTRODUCTION 1 1.1 Neuroendocrine Tumours 1 1.1.1 Definition and History of the Diffuse Neuroendocrine System 1 1.1.2 Short History of Neuroendocrine Tumours 2 1.1.3 Features of the Diffuse Neuroendocrine System 2 1.1.4 Epidemiology of Tumours 3 1.1.5 Classification of Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETs) 3 1.1.6 Clinical Presentation 5 1.1.7 Treatment 5 1.2 Drug Resistance 6 1.2.1 ATP-Binding Cassette Transporter 6 1.2.2 pH and Drug Resistance 7 1.2.3 pH Regulation of Intracellular Compartments 8 1.2.3.1 Vacuolar Adenosine Triphosphatase (v-ATPase) 8 1.2.3.2 Voltage-Gated Chloride Channels (ClC-channels) 9 1.2.4 V-ATPase and ClC-Channels in Cancer and Drug Resistance 12 1.3 Etoposide 12 1.4 Aim of this Study 13 2 MATERIALS AND METHODS 14 2.