Yan Julia Fangfei, Kim Hoguen, Jeong Seul-Ki, Lee Hyoung-Joo, Sethi Manveen K, Lee Ling Y, Beavis Ronald C, Im Hogune, Snyder Michael P, Hofree Matan, Ideker Trey, Wu Shiaw-Lin, Paik Young-Ki, Fanayan Susan, Hancock William S
Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
Yonsei University College of Medicine, Yonsei University , 50-1 Yonsei-Ro, Seodaemun-gu, Seoul 120-752, Korea.
J Proteome Res. 2015 Dec 4;14(12):4995-5006. doi: 10.1021/acs.jproteome.5b00827. Epub 2015 Oct 20.
V-erb-b2 erythroblastic leukemia viral oncogene homologue 2, known as ERBB2, is an important oncogene in the development of certain cancers. It can form a heterodimer with other epidermal growth factor receptor family members and activate kinase-mediated downstream signaling pathways. ERBB2 gene is located on chromosome 17 and is amplified in a subset of cancers, such as breast, gastric, and colon cancer. Of particular interest to the Chromosome-Centric Human Proteome Project (C-HPP) initiative is the amplification mechanism that typically results in overexpression of a set of genes adjacent to ERBB2, which provides evidence of a linkage between gene location and expression. In this report we studied patient samples from ERBB2-positive together with adjacent control nontumor tissues. In addition, non-ERBB2-expressing patient samples were selected as comparison to study the effect of expression of this oncogene. We detected 196 proteins in ERBB2-positive patient tumor samples that had minimal overlap (29 proteins) with the non-ERBB2 tumor samples. Interaction and pathway analysis identified extracellular signal regulated kinase (ERK) cascade and actin polymerization and actinmyosin assembly contraction as pathways of importance in ERBB2+ and ERBB2- gastric cancer samples, respectively. The raw data files are deposited at ProteomeXchange (identifier: PXD002674) as well as GPMDB.
V- erb-b2成红细胞白血病病毒癌基因同源物2,即ERBB2,是某些癌症发生发展过程中的一个重要癌基因。它可与其他表皮生长因子受体家族成员形成异二聚体,并激活激酶介导的下游信号通路。ERBB2基因位于17号染色体上,在一部分癌症(如乳腺癌、胃癌和结肠癌)中会发生扩增。以染色体为中心的人类蛋白质组计划(C-HPP)特别感兴趣的是其扩增机制,该机制通常会导致ERBB2附近的一组基因过表达,这为基因定位与表达之间的联系提供了证据。在本报告中,我们研究了ERBB2阳性患者样本以及相邻的对照非肿瘤组织。此外,选择不表达ERBB2的患者样本作为对照,以研究该癌基因表达的影响。我们在ERBB2阳性患者肿瘤样本中检测到196种蛋白质,这些蛋白质与非ERBB2肿瘤样本的重叠极少(29种蛋白质)。相互作用和通路分析确定,细胞外信号调节激酶(ERK)级联以及肌动蛋白聚合和肌动球蛋白组装收缩分别是ERBB2阳性和ERBB2阴性胃癌样本中的重要通路。原始数据文件已存于ProteomeXchange(标识符:PXD002674)以及GPMDB中。