Abstract 1852: Merlin/NF2 is associated with elevated aromatase expression and estrogen formation in human liver tissues and liver cancer cells: An unifying model for hepatocellular carcinoma development and progression

It is recognized that the product of neurofibromatosis type 2 (NF2) tumor suppressor gene, also referred to as Merlin/neurofibromin, is implicated in the homeostatic regulation of the liver stem cell niche through the control of abundance and signaling of epidermal growth factor receptor (EGFR), with a mechanism independent of the Mst/Lats/Yap Hippo pathway [1]. We have previously reported that locally elevated estrogen formation, driven by abnormally high expression and function of the aromatase enzyme, may be implicated in both development and progression of human hepatocellular carcinoma (HCC) through the activation of a rapid signaling pathway mediated by amphiregulin (AREG) and EGFR [2]. In this framework, we have recently presented a model by which the aromatase-estrogen-amphiregulin-EGFR axis is activated in response to tissue injury and/or inflammatory disease, with its alteration eventually leading to development not only of major human tumors (liver, breast, prostate), but also to other non-neoplastic diseases, including type 2 diabetes, obesity, Alzheimer's disease, heart disease and stroke [3]. In the present work, we have investigated the expression of merlin/neurofibromin (NF2) in different liver cancer cells and liver tissues in relation to aromatase expression/function, estrogen receptor (ER) status, amphiregulin and EGFR. Our data indicate that NF2 expression is strictly associated to aromatase, AREG and EGFR expression, being elevated in HCC tissues and HepG...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Endocrinology Source Type: research