Role of growth factor and cytokine singaling in the determination of mammary epithelial cell characteristics

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Ehime University
• Principal Investigator: FUKUDA Shinji 愛媛大学, プロテオサイエンスセンター, 講師 (70398238)
• Co-Investigator(Renkei-kenkyūsha): HIGASHIYAMA Shigeki 愛媛大学, プロテオサイエンスセンター, 教授 (60202272) ; TAKEMORI Nobuaki 愛媛大学, プロテオサイエンスセンター, 講師 (40533047)
• Research Collaborator: FUKUDA Hisayo 愛媛大学, 医学部, 研究員
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 乳腺細胞 / EGF受容体 / 上皮間葉転換

Outline of Final Research Achievements

The family of EGF ligands and the EGF receptor (EGFR) signaling system is crucial for numerous physiological and pathological events. EGF and amphiregulin (AREG) share a common EGFR, but they are capable of inducing distinctly different biological outcomes. Here, we found that EGF and AREG reversibly interconverted two distinct phenotypes of MCF10A. They differed in the expression of epithelial-mesenchymal transition (EMT) markers, the mode of cell migration and the ability for acinus-formation. We also found that ligand-switching between EGF and AREG transiently altered the integrated signal strength of the shared EGFR-MEK1-ERK2 pathway, thereby reversing the relative expression levels of a downstream EMT regulator, ZEB1, miR-205 and miR-200c. These results suggest that cognate EGFR ligands sharing the same signaling molecules could reversibly interconvert mammary epithelial cell phenotypes through the control of signal strength.

Free Research Field

分子細胞生物学