TY - JOUR T1 - Endoplasmic Reticulum Stress in Pancreatic Neuroendocrine Tumors is Linked to Clinicopathological Parameters and Possible Epigenetic Regulations JF - Anticancer Research JO - Anticancer Res SP - 6127 LP - 6136 VL - 35 IS - 11 AU - ECKHARD KLIESER AU - ROMANA ILLIG AU - STEFAN STÁTTNER AU - FLORIAN PRIMAVESI AU - TARKAN JÁGER AU - STEFAN SWIERCZYNSKI AU - TOBIAS KIESSLICH AU - RALF KEMMERLING AU - CARMEN BOLLMANN AU - PIETRO DI FAZIO AU - DANIEL NEUREITER Y1 - 2015/11/01 UR - http://ar.iiarjournals.org/content/35/11/6127.abstract N2 - Background: Endoplasmic reticulum (ER) stress is a highly-conserved cellular defense mechanism in response to perturbations of ER function. The role of ER stress in pancreatic neuroendocrine tumors (pNET) still remains unclear. Materials and Methods: We analyzed the protein expression pattern of the four key players of ER stress, (chaperone binding imunoglobluin protein (BiP), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4) and caspase 4) as well as histone deacetylases (HDACs) by a tissue microarray (TMA) of 49 human pNET resected between 1997 and 2013 following, extensive clinicopathological characterization. Results: Immunohistochemical profiling revealed a significant up-regulation of BiP, ATF4, CHOP and caspase 4 in pNET cases compared to normal controls. Correlated to clinicopathological parameters especially BiP expression could be linked to higher grading and proliferation as well as to lower survival probability. Finally, expression of ER stress markers correlated with HDAC expression in situ and pharmalogical inhibition by panobinostat significantly reduced cell viability in vitro. Conclusion: Up-regulation of ER stress in pNET indicates the presence and engagement of ER stress signaling in this tumor entity demonstrating another possible anticancer therapy option in pNET. ER -