Elucidation of the association between cell morphology and PI3K gene mutations in mammary apocrine carcinoma.

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K15096
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Nihon University (2021-2023); St. Luke's International University (2018-2020)
• Principal Investigator: NOZAKI Fumi 日本大学, 医学部, 助教 (10409021)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 乳癌 / アポクリン癌 / PI3K

Outline of Final Research Achievements

PIK3CA gene hot spot mutations were found in 3/20 (15.0%) of human breast cancer surgical specimens apocrine carcinoma. Although we succeeded in introducing the PIK3CA gene hot spot mutation in nonapocrine carcinoma cell cultures, we were unable to establish mutant cell lines, and thus were unable to observe cell morphological changes with or without the PIK3CA gene mutation. In order to investigate whether the suppression of PIK3CA gene expression suppresses cell proliferation, we performed PIK3CA gene knockdown experiments using two types of apocrine carcinoma cells with PIK3CA gene mutation (PIK3CA gene mutation+) and one control cell type (PIK3CA gene mutation-). The PIK3CA gene knockdown experiment was performed using only the former two types of cells.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

培養細胞においては、PI3K阻害薬のIC50(50％阻害濃度)はPIK3CA遺伝子変異を有する乳癌培養細胞株で低いことより、PIK3CA遺伝子変異は PI3K阻害薬の効果を予測するバイオマーカーとして知られている。PIK3CA遺伝子変異の有無による細胞形態の変化の観察には至らなかったが、ヒト乳癌手術検体アポクリン癌においてPIK3CA遺伝子変異が認められたこと、PIK3CA遺伝子のノックダウンによりアポクリン癌培養細胞増殖が抑制されたことより、アポクリン癌はPIK3分子生物薬などの治療標的となる可能性があることが示された。