Characterization and drug screening of small intestinal adenocarcinoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590931
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: ATSUO Yamada 東京大学, 医学部附属病院, 助教 (80534932)
• Co-Investigator(Kenkyū-buntansha): HIRATA Yoshihiro 東京大学, 医学部附属病院, 特任講師 (10529192)
• Research Collaborator: SUZUKI Hirobumi 東京大学, 医学部附属病院, 特任臨床医
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 小腸癌 / 遺伝子変異 / 抗癌剤

Outline of Final Research Achievements

Small bowel adenocarcinoma (SBA) is rare malignancy with a poor prognosis and its pathogenesis remains unclear. The aims of this study were to investigate the molecular mechanisms and discover new treatments of SBA by establishing SIAC1cells. SIAC1 cells showed small intestinal cell phenotype, decreased MMR proteins with CpG methylator phenotype and frame-shift mutations of target genes. SIAC1 cells had aβ-catenin deletion, which results in a stable β-catenin protein with enhanced Wnt signaling. Clinical SBA samples also showed β-catenin deletion, aberrant MMR proteins expression and frame-shift mutations of MSI target genes. Screening assay using 140 compounds showed that eribulin significantly inhibited SIAC1 cell growth by inhibition of Wnt signaling through β-catenin protein degradation. This drug also showed efficacy in nude mice with SIAC1 cell xenograft, Eribulin, which showed anti-cancer effect both in vitro and in vivo, might be a good candidate for SBA treatment.

Free Research Field

医歯薬学