PMID- 31466817 OWN - NLM STAT- MEDLINE DCOM- 20200227 LR - 20200227 IS - 1618-0631 (Electronic) IS - 0344-0338 (Linking) VI - 215 IP - 10 DP - 2019 Oct TI - Over expression of amphiregulin promoted malignant progression in gastric cancer. PG - 152576 LID - S0344-0338(19)30781-2 [pii] LID - 10.1016/j.prp.2019.152576 [doi] AB - Human Amphiregulin (AREG) was found to be over expressed in many types of cancer patients including gastric cancer (GC). However, its role in GC development remained unknown. In this study, over expression of AREG in MGC803 and SGC7901 GC cells were conducted by gene transfection through utilizing gateway recombinant cloning technology. Meanwhile, AREG knocked down in BGC823 and MKN45 GC cells were achieved by lentvirus-mediated shRNA oligos infection. The results showed that over expression of AREG promoted cancer cells proliferation, invasion and migration, prevented apoptotic cell death and facilitated cell cycle progression. However, the above AREG-mediated oncogenic phenotypes were reversed while AREG was knocked down in cancer cells. Furthermore, the expression of AREG in GC cells was associated with higher level of activation of both ERK/JNK/p38 and PI3K/Akt signaling pathways, which were also diminished by AREG knocked down. Finally, the result from study in vivo showed that the silencing AREG expression by AREG knocked down inhibited tumor growth in nude mice. Collectively, the data provided a convincingly laboratory evidence that over expression of AREG promoted malignant procession via activation of ERK/JNK/p38 and PI3K/Akt signaling pathways. Thus AREG possessed an oncogenic activity and could be served as a target for gastric cancer therapy. CI - Copyright (c) 2019 The AoYang Cancer Research Institute of Jiangsu University. Published by Elsevier GmbH.. All rights reserved. FAU - Jiang, Jiajia AU - Jiang J AD - The AoYang Cancer Research Institute of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, China. FAU - Zhao, Wei AU - Zhao W AD - Department of Pathology, Nanjing Medical University, Nanjing, 210029, China; Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, 210029. China; Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029. China. FAU - Tang, Qi AU - Tang Q AD - Department of Pathology, Nanjing Medical University, Nanjing, 210029, China; Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, 210029. China; Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029. China. FAU - Wang, Bing AU - Wang B AD - Department of Oncology, Affiliated AoYang Hospital of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, China. FAU - Li, Xiaohua AU - Li X AD - The AoYang Cancer Research Institute of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, China; National Center of Gene Testing Technology Application & Demonstration, Anhui, 230088, China; The Laboratory of Clinical Genomics, KingMed Diagnostics Group, Hefei, 230088, China. Electronic address: joshua28li@163.com. FAU - Feng, Zhenqing AU - Feng Z AD - The AoYang Cancer Research Institute of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, China; Department of Pathology, Nanjing Medical University, Nanjing, 210029, China; Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, 210029. China; Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029. China. Electronic address: fengzhenqing@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20190810 PL - Germany TA - Pathol Res Pract JT - Pathology, research and practice JID - 7806109 RN - 0 (Amphiregulin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Amphiregulin/genetics/*metabolism MH - Apoptosis/physiology MH - Cell Line, Tumor MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - Disease Progression MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction/*physiology MH - Stomach Neoplasms/genetics/*metabolism/pathology OTO - NOTNLM OT - Amphiregulin OT - Cell signaling OT - Gastric cancer OT - Oncogenic progression EDAT- 2019/08/31 06:00 MHDA- 2020/02/28 06:00 CRDT- 2019/08/31 06:00 PHST- 2019/04/25 00:00 [received] PHST- 2019/07/17 00:00 [revised] PHST- 2019/07/31 00:00 [accepted] PHST- 2019/08/31 06:00 [pubmed] PHST- 2020/02/28 06:00 [medline] PHST- 2019/08/31 06:00 [entrez] AID - S0344-0338(19)30781-2 [pii] AID - 10.1016/j.prp.2019.152576 [doi] PST - ppublish SO - Pathol Res Pract. 2019 Oct;215(10):152576. doi: 10.1016/j.prp.2019.152576. Epub 2019 Aug 10.