Iijima Mariko, Anai Motonobu, Kodama Tatsuhiko, Shibasaki Yoshikazu
Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
Biochem Biophys Res Commun. 2017 Jul 15;489(1):83-88. doi: 10.1016/j.bbrc.2017.03.006. Epub 2017 Mar 6.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in many cellular functions including cell growth and migration. EGFR may be activated by EGF family ligands such as EGF and epiregulin (EREG). EREG is overexpressed in human colon and breast cancers, implying that EREG plays roles in tumorigenesis. Although EGF family members share a receptor, it is not well known whether their signaling pathways differ. In order to investigate EREG signaling, we established the anti-EREG antibody that inhibits EGFR downstream signaling stimulated by EREG but not by EGF. While the anti-EREG antibody has little effect on cell growth, it inhibits cell adhesion of EREG-expressing autocrine cancer cell lines. Our results suggest that anti-EREG antibodies represent valuable tools for elucidating EREG-specific signaling pathways, and may serve as therapeutic candidates for the treatment of cancers.
表皮生长因子受体(EGFR)是一种受体酪氨酸激酶,参与包括细胞生长和迁移在内的许多细胞功能。EGFR可被表皮生长因子(EGF)家族配体如EGF和上皮调节素(EREG)激活。EREG在人类结肠癌和乳腺癌中过度表达,这意味着EREG在肿瘤发生中发挥作用。尽管EGF家族成员共享一个受体,但它们的信号通路是否不同尚不清楚。为了研究EREG信号传导,我们制备了一种抗EREG抗体,该抗体可抑制由EREG而非EGF刺激的EGFR下游信号传导。虽然抗EREG抗体对细胞生长影响很小,但它可抑制表达EREG的自分泌癌细胞系的细胞黏附。我们的结果表明,抗EREG抗体是阐明EREG特异性信号通路的有价值工具,并且可能作为癌症治疗的候选药物。