Development of a novel anti-cancer therapeutics targeting HB-EGF

2016 Fiscal Year Final Research Report

• Project/Area Number: 26250033
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: MEKADA EISUKE 大阪大学, 微生物病研究所, 教授 (20135742)
• Co-Investigator(Renkei-kenkyūsha): IWAMOTO Ryo 大阪大学, 微生物病研究所, 准教授 (10213323) ; MIZUSHIMA Hiroto 大阪大学, 微生物病研究所, 助教 (30379094) ; NAKAMURA Takashi 大阪大学, 微生物病研究所, 研究員 (00570673)
• Research Collaborator: YONEDA Tomoko 大阪大学, 微生物病研究所, 特任技術職員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: EGFR / HB-EGF / ErbB4 / 増殖抑制

Outline of Final Research Achievements

HB-EGF plays an indispensable role in suppression of cell proliferation in mouse valvulogenesis. However, ligands of the EGF receptor (EGFR/ErbB1), including HB-EGF, are generally considered as growth-promoting factors, as shown in cancers. We investigated the role of ErbB receptors in valvulogenesis in vivo using ErbB1- and ErbB4-deficient mice, and an ex vivo model of endocardial cushion explants. We found that HB-EGF suppresses valve mesenchymal cell proliferation through a heterodimer of ErbB1 and ErbB4, and an ErbB1 ligand(s) promotes cell proliferation through a homodimer of ErbB1. Our study demonstrates that opposing signals generated by different ErbB dimer combinations function in the same cardiac cushion mesenchymal cells for proper cardiac valve formation.

Free Research Field

細胞生物学、腫瘍生物学