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- Title
CUX1 Mediates Progression of Neuroendocrine Tumors.
- Authors
Krug, S.; Kühnemuth, B.; Griesmann, H.; Kortenhaus, J.; Lankat-Buttgereit, B.; Fendrich, V.; Gress, T.; Michl, P.
- Abstract
Introduction: CUX1 is a key mediator of tumor progression in pancreatic ductal adenocarcinoma (PDAC) and is upregulated during tumorigenesis in PDAC. It contributes to tumor invasion and is resistant to apoptosis and angiogenesis. Aim(s): To characterize the effects of CUX1 in neuroendocrine tumors (NETs). Materials and methods: The effect of CUX1 on proliferation/apoptosis was analysed using knock-down and overexpression strategies in neuroendocrine Bon-1/Insl-cell-lines. Conditioned medium of CUX1 overexpressing Bon-1/Insl-cells was collected for functional assays. CUX1 expression in human and murine insulinomas was evaluated using immunohistochemistry (IHC) and quantitative RT-PCR. Results: Knock-down of CUX1 facilitated apoptosis and decreased proliferation in Bon-1/Ins-cells, overexpressing of CUX1 offered inversed effects. CUX1 IHC showed intense staining in the maioritiy of analysed human insulinomas. In the murine tumor progression model of insulinomas (RIP-Tag model), CUX1 expression increased over time, paralleled by histological progression of islet cell hyperplasia to invasive instdinoma. Furthermore, conditioned medium of CUX1 overexpressing Bon-1/Insl-cells stimulated migration and tube formation of endothelial cells, indicating a proangiogenic effect of the CUXl-dependent secretome. Conclusion: CUX1 is identified as a mediator of proliferation, apoptosis and angiogenesis in vitro, is highly expressed in human NETs and correlates with tumor progression in a murine neuroendocrine tumor model.
- Subjects
NEUROENDOCRINE tumors; IMMUNOHISTOCHEMISTRY; CELLULAR pathology; CANCER invasiveness; PANCREATIC duct; CANCER
- Publication
Neuroendocrinology, 2012, Vol 96, p7
- ISSN
0028-3835
- Publication type
Article