%0 Journal Article
%T Involvement of Cell Proliferation Induced by Dual Intracellular Signaling of HB-EGF in the Development of Colitis-Associated Cancer during Ulcerative Colitis
%A Satoshi Tanida
%A Tsutomu Mizoshita
%A Takashi Mizushima
%A Takaya Shimura
%A Takeshi Kamiya
%A Hiromi Kataoka
%A Takashi Joh
%J Ulcers
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/457637
%X In ulcerative colitis (UC), the duration and severity of inflammation are responsible for the development of colorectal cancer. Reactive oxygen species (ROS), reactive nitric metabolites (RNMs) and interleukin (IL)-8, released by epithelial and immune cells, are involved in the pathogenesis of colitis-associated cancer. Nitric oxide and peroxynitrite activate epidermal growth factor receptor (EGFR), and therapeutic agents targeted towards EGFR are currently used to treat advanced colorectal cancer. IL-8 (a G-protein coupled receptor (GPCR) agonist), which is involved in neutrophil recruitment and activation in persistent active colitis, also promotes cleavage of the proheparin-binding epidermal growth factor-like growth factor (proHB-EGF) through a disintegrin and metalloproteinase (ADAM). The cleaved HB-EGF and C-terminal fragments (intracellular CTF) regulate proliferation via EGFR activation and nuclear export of promyelocytic leukemia zinc finger, transcription repressor, respectively. Here, we focus on the mechanisms by which RNM- and IL-8-induced EGF signaling regulate cell proliferation during the development of colitis-associated cancer.
%U http://www.hindawi.com/journals/ulc/2011/457637/