title: Effect of REG Iα protein on angiogenesis in gastric cancer tissues.
abstract: Regenerating gene (REG) Iα is not only overexpressed in a subset of gastric cancers, but also involved in tumor progression. However, the mechanism by which (REG) Iα promotes tumor growth is not fully understood. In the present study, we investigated whether REG Iα plays a role in angiogenesis during the progression of gastric cancers. Expression of REG Iα and its receptor (EXTL3; exostoses like-3) was examined using immunohistochemistry in specimens of human gastric cancer. Microvessel density (MVD) in gastric cancer tissues was evaluated using an image analysis system after CD34 immunostaining. Relationships among clinicopathological features, REG Iα expression and MVD in gastric cancer tissues were analyzed. Effects of REG Iα protein on HUVEC cells in terms of proliferation and anti-apoptosis were assessed by WST-1 assay and FACS, respectively. Furthermore, the intracellular signaling by which REG Iα exerts its biological roles was examined in vitro. REG Iα expression was significantly related to lymph node metastasis and its receptor EXTL3 was ubiquitously expressed in not only the tumor cells, but also the tumor vessel cells in the gastric cancer tissues. MVD was significantly higher in gastric cancers that were REG Iα-positive than in those that were negative. Treatment with REG Iα protein promoted growth and anti-apoptosis through activation of the ERK and Akt signaling pathways in HUVEC cells, whereas these effects were attenuated by treatment with anti-REG Iα -antibody. REG Iα protein may play a role in angiogenesis during progression of gastric cancer.
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Ken
authors: K
authors: Hara
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Hirokazu
authors: H
authors: Fukui
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Chao
authors: C
authors: Sun
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Yoshitaka
authors: Y
authors: Kitayama
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Hirotsugu
authors: H
authors: Eda
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Takahisa
authors: T
authors: Yamasaki
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Takashi
authors: T
authors: Kondo
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Toshihiko
authors: T
authors: Tomita
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Tadayuki
authors: T
authors: Oshima
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Jiro
authors: J
authors: Watari
authors: Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan.
authors: Takahiro
authors: T
authors: Fujimori
authors: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Hiroto
authors: H
authors: Miwa
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051847:Lithostathine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*
chemical_list: C110774:EXTL3 protein, human; D051847:Lithostathine; C497617:REG1A protein, human; D017351:N-Acetylglucosaminyltransferases