2021 Fiscal Year Final Research Report
Role of proline isomerase in ER-positive breast cancer and its potential as a therapeutic target
Project/Area Number |
20K16333
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 50010:Tumor biology-related
|
Research Institution | Yamaguchi University |
Principal Investigator |
Habara Makoto 山口大学, 共同獣医学部, 助教(特命) (60846525)
|
Project Period (FY) |
2020-04-01 – 2022-03-31
|
Keywords | ER陽性乳癌 / 乳癌 / プロリン異性化酵素 / エストロゲン受容体 / ER / FKBP / FKBP52 / FKBP51 |
Outline of Final Research Achievements |
We identified FK506-binding protein 52 (FKBP52) as a factor associated with poor prognosis of individuals with ER(estrogen receptor; ER induces cell proliferation and exhibits increased expression in a large subset of breast cancers)-positive breast cancer by comprehensive life-science database analysis. FKBP52 is classified as a peptidyl proline isomerase that regulates protein function. Inhibition of FKBP52 in ER-positive breast cancer cells decreased ER expression by promoting its degradation and markedly reduced cell proliferation. Furthermore, the tumor suppressive effect of FKBP52 inhibition was also observed in endocrine therapy-resistant breast cancer cells and in xenograft mice. FKBP52 stabilizes ER by promoting the binding of BRCA1 to the ER.
|
Free Research Field |
腫瘍生物学
|
Academic Significance and Societal Importance of the Research Achievements |
エストロゲン受容体(ER)は乳癌の増殖制御因子であり内分泌治療の主要な標的だが、ERの活性を上昇させる分子機構はまだ十分に解明されていない。本研究ではFKBPによるERの新たな制御機構を明らかにした。更にFKBP52阻害は内分泌治療抵抗性の乳癌細胞においても抗腫瘍効果を示すことから、新たなバイオマーカー、治療法開発に繋がることが期待できる。 FKBP52と癌との関連性については報告が少ない。本研究が明らかにしたFKBP52による癌の増殖制御はプロリン異性化の癌における役割を新たに示し、生体内におけるプロリン異性化の意義の理解に繋がるものである。
|