Are eIFs crucial in neuroendocrine tumorigenesis?

Introduction: Neuroendocrine tumors (NETs) can develop in almost any organ, therefore they are a very heterogeneous group of tumors. One major activity in each cell is translation of mRNA to the corresponding protein, which plays an important role in cancer development. Crucial for this translation process are eukaryotic initiation factors (eIFs), which are themselves regulated by the mammalian target of Rapamycin (mTOR)-pathway. Mutation or deregulated expression of eIFs influence cell growth and proliferation, contributing to carcinogenesis. The incidence of NETs has increased fivefold over the last three decades.

Aim(s): We investigated the contribution of eIFs to NETs.

Materials and methods: Gastroenteropancreatic NETs and their corresponding liver metastases from 4 individuals were analyzed on protein expression level for various eIFs and mTOR members by Western Blot. Normal adjacent tissue served as control.

Results: Indeed, eIFs and members of the mTOR pathway were differentially expressed in NETs, and were changed in NET cell lines pointing to a possible mechanistic link between NETs and mTOR.

Conclusion: eIFs are altered in primary NET tumors, however compared to primary NETs, liver metastases display less alterations of eIF expression. A strong difference in protein expression difference between primary tumor and metastases was found. Our data indicate a contribution of eIFs and mTOR signaling to the development and progression of NETs. A better understanding of the molecular mechanisms leading to neuroendocrine tumorigenesis is crucial for establishing novel and tailored treatment strategies for NET patients.

Keywords: nets, mtor, eukaryotic translation initiation.