Forkheadbox Proteins as Novel Drug Targets in Gastroenteropancreatic Neuroendocrine Tumor Disease: Inhibition of FoxM1 Exerts Antiproliferative Effects in GEP-NEN Cell Lines

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Introduction: Forkheadbox proteins (Fox proteins) are transcriptions factors. They are highly conserved key players in a large number of cellular processes. Fox proteins have been described as acting as both tumor suppressors and oncogenes. Most notably, they operate in the context of the majority of cancer-related pathways. Information about the fuunction of these proteins in gastroenteropancreatic neuroendocrine neoplasias is scant.

Aim(s): Therefore, we assessed FoxM1 expression in a series of GEP-NENs and studied the effects of FoxM1 inhibition in human GEP-NEN cell lines.

Materials and methods: Tumor specimens from 206 patients (61 G1, 105 G2, 40 G3 tumors) from two institutions (Charité-CBF; FSU Jena) were studied immunohistochemically for FoxM1 expression. The cell lines BON, QGP-1, KRJ-1 and LCC18 were treated with Siomycin A, a specific FoxM1 inhibitor, and FoxM1 specific siRNA. Treated cells were analyzed by proliferation assays and western blot. Microarrays with treated v. untreated cells are planned further on.

Conference: 11th Annual ENETSConcerence (2014)

Presenting Author: Briest F

Authors: Briest F, Freitag H, Lewens F, Kaemmerer D, Hörsch D,

Keywords: Forkheadbox proteins, signalling network, immunohistochemistry, siRNA, microarray technique,