The active chromatin domain that is regulated by the non-coding RNAs in recurrent breast cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04744
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Japanese Foundation for Cancer Research (2017-2018); Kumamoto University (2016)
• Principal Investigator: Saitoh Noriko 公益財団法人がん研究会, がん研究所 がん生物部, 部長 (40398235)
• Research Collaborator: YAMAMOTO tatsuro ; SAKAMOTO chiyomi ; TACHIWANA hiroaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 非コードRNA / クロマチン / 細胞核 / 乳がん

Outline of Final Research Achievements

Approximately 70% of breast cancers is estrogen receptor (ER)-positive, which highly express the ER protein. The endocrine therapy that inhibits estrogenic action is effective for this type of breast cancer, however, the cancer acquires the therapy resistance after long term of the treatment, resulting in recurrence. In this study, using the endocrine-therapy resistant breast cancer cell model, I have revealed a molecular mechanism underlying the overexpression of ESR1, the gene for ER during the acquisition of the therapy resistance. I found that the non-coding RNAs, Eleanors regulate the mega-base chromatin domain and expression of the multiple genes involving breast cancer including ESR1.

Free Research Field

分子細胞生物学、がん生物学

Academic Significance and Societal Importance of the Research Achievements

遺伝子の発現制御はほぼ全ての生命現象に重要で、その異常はがんを含む疾患に深く関わる。本研究成果では、乳がんに重要なESR1遺伝子の発現が非コードRNAエレノアによるクロマチンドメインの制御を介して行われるという、学術的に新しい知見を得られた。また、非コードRNAを標的とする再発乳がんの診断や治療への道筋をつける成果を得た。