engleski

The role of cytokines and their polymorphisms in the gastroenteropancreatic neuroendocrine tumors (GEP-NETs): mini review

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare, heterogeneous group of tumors arising from the enteroendocnne cells of the diffuse endocrine system (DES). Their incidence ranges from 2.4 per 100.000 people for carcinoids and is even less frequent for pancreatic endocrine tumors. Usually, these tumors occur sporadically, but in some instances are a part of multiple endocrine neoplasia syndromes such as MEN-1, neurofibromatosis type 1 (NF-1) or von Hippel Lindau disease (VHL), when they are accompanied by adenomas/hyperplasia of other endocrine tissues. The true genetic background of the mentioned tumors has been extensively studied, especially in GEP-NETs occurring as a part of MEN-1 syndrome (parathyroid hyperplasia/ hyperparathyroidism, pancreatic endocrine tumors, pituitary adenomas and adrenal cortical adenomas), and a tumor suppressor gene encoding protein menin has been identified on 11q13. Menin has primarily nuclear localization and it appears to regulate DNA transcription/translation and participate in cell cycle regulation through interactions with NF-κB proteins. Mutations of MEN-1 gene are not as frequent among sporadic GEP-NETs, so further investigation of more prevalent genes of low to mediate penetrance, which would play a role in the genetic predisposition to, and disease progression of, GEP-NETs is needed. As GEP-NETs, besides hormones and biogenic amines, produce growth factors and cytokines which modulate tumor cell growth and differentiation, a new highlight is put on the investigation of cytokine and growth factor gene polymorphisms, especially ILs, PDGF, IGF, FGF, TNF-α, VEGF, TGF-α and TGF-β genes. These cytokines and growth factors may be responsible not only for the NET cell crosstalk but also, acting on autocrine and paracrine loops for the interaction of immunocytes, endothelial cells, non-NET epithelial cells and neurons with NETs, thus contributing to GEP-NET development and progression.

cytokines; GEP-NETs

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