Tumorigenesis by transcriptional suppression of Breast cancer 2, early onset (BRCA2) by ANXA2

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Kitasato University
• Principal Investigator: Yoshikawa Yasunaga 北里大学, 獣医学部, 准教授 (00552043)
• Co-Investigator(Kenkyū-buntansha): 佐々木 宣哉 北里大学, 獣医学部, 教授 (20302614)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ANXA2 / BRCA2 / 転写 / プロモーター活性 / 乳腺腫瘍 / DNA損傷修復 / 発現抑制 / 発現調節

Outline of Final Research Achievements

We have shown that mutations or decreased expression of the tumor suppressor gene BRCA2 is involved in the development of canine mammary gland tumors. While performing these studies, we found that ANXA2 may interact with novel BRCA2 silencer region and be involved in the BRCA2 transcriptional suppression mechanism. This study aimed to elucidate the possibility that BRCA2 was suppressed by ANXA2. The ANXA2 knockout HeLa cells showed increased sensitivity against the BRCA2-related DNA-damaging agents. However, reduced ANXA2 protein level was not influenced the BRCA2 protein expression. Therefore, we expected that ANXA2 itself contributes to DNA damage repair and performed functional analysis of ANXA2. However, we could not demonstrate how ANXA2 contributes to DNA damage repair in this study. Further analyses are required to reveal the function of ANXA2 in DNA damage repair.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、ANXA2がどの様にDNA損傷修復に関与するかを解明する事はできなかったが、ANXA2をノックアウトするとBRCA2が関わるDNA損傷剤に対して高感受性になる事が分かった。この結果は、多機能タンパク質であるANXA2の新たな機能を見出す手がかりになると考えられる。また、ANXA2が抗癌治療のターゲットになる可能性を示唆している。