Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells

摘要: The product of neurofibromatosis type 2 (NF2) gene, also known as Merlin/neurofibromin 2, homeostatically regulates liver stem cells by controlling abundance and signaling epidermal growth factor receptor (EGFR), with a mechanism independent the Hippo pathway. We have reported that locally elevated estrogen formation, driven abnormally high expression function aromatase, may be implicated in development progression human hepatocellular carcinoma (HCC) through activation rapid pathway mediated amphiregulin (AREG) EGFR. recently presented model which aromatase-estrogen-amphiregulin-EGFR axis is activated response to tissue injury and/or inflammatory disease, its alteration eventually leading major tumors (liver, breast, prostate) other chronic diseases (diabetes, obesity, Alzheimer's heart disease). In this study, we investigated NF2 cancer tissues relation aromatase expression/function, (ER) status amphiregulin. Our data indicate associated AREG expression, being HCC HepG2 cells, intermediate cirrhotic Huh7 lower nontumoral HA22T cells. addition, inversely related wild hERα66 proportional membrane-associated hERα36 splice variant, measured exon-specific RT-PCR analysis, both vivo vitro. Furthermore, incubation estradiol induced significant decrease (over 54% 22%, respectively), while no change could observed effect activity cell lines. Based on above combined evidence, hypothesize behaves protein sensing damage aromatase-driven local regulation differentiation repair.