Chromosomal instability and the development of multiple cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10562
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Jichi Medical University
• Principal Investigator: Noda Hiroshi 自治医科大学, 医学部, 准教授 (00382937)
• Co-Investigator(Kenkyū-buntansha): 鈴木 浩一 自治医科大学, 医学部, 准教授 (70332369) ; 力山 敏樹 自治医科大学, 医学部, 教授 (80343060)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 多発癌 / セントロメア / 脱メチル化異常 / 染色体不安定性 / Satellite α transcript

Outline of Final Research Achievements

We constructed lentiviral vectors expressing satellite alpha transcript (SAT) and control viruses and then infected human mammary epithelial cells with these vectors. Immunocytochemistry revealed that the incidence of segregation errors including abnormal segregation, micronuclei and anaphase bridge was significantly higher in the cells overexpressing SAT than in the controls. Then we constructed lentiviral vectors expressing mouse major satellite and infected the mouse model developing breast cancer. We assess how intraductal administration of these vectors into the mouse mammary gland induces multiple breast cancer via chromosomal instability.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

組織のみならず非癌部組織でも亢進しています。単発癌に比べて多発癌の非癌部背景組織で有意に高い事より、SatAは「field cancerization」に働き、大腸癌、乳癌の多発発生に関わっている可能性が考えられます。昨今の縮小手術の普及は異時性発癌のリスクを助長すると懸念され、その機序の解明は喫緊の課題です。本研究では、SatAが関わる多発癌発生の機序を明らかにします。