Role of the alternation of steroid hormone level in the response and resistance to endocrine therapy for breast cancer

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10059
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Saji Shigehira 福島県立医科大学, 医学部, 主任教授 (80446567)
• Co-Investigator(Renkei-kenkyūsha): OHTAKE Toru 福島県立医科大学, 医学部・乳腺外科学講座, 主任教授 (50363750) ; SATO Fumiaki 京都大学, 医学研究科・乳腺外科学, 准教授 (20467426)
• Research Collaborator: SUGA Junko 福島県立医科大学, 医学部・腫瘍内科学講座, 研究生 ; TANAKA Nobuyuki 宮城県立がんセンター研究所, がん先進医療開発研究部, 部長
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 乳癌 / エストロゲン / エストロゲン受容体 / HER3

Outline of Final Research Achievements

Endocrine therapy to estrogen receptor (ER) positive breast cancer is the most important modality, since about 75% of newly diagnosed breast cancer is ER-positive. We explore the response and resistance related factors in terms of the alternation of steroid hormone level. From our several background experiments using cell study, we found that alternation of estradiol (one of estrogens) level affects the degradation speed of HER3. HER3 is one of membrane receptors which contributes to aggressiveness of breast cancer and resistance to endocrine therapy. We showed that enhanced degradation of HER3 depends on ubiquitin-proteasome pathway and specific E3-ligase, Nedd4-1, which also regulates degradation of ER. From these findings, we speculate that estradiol, ER and HER3 have crosstalk through regulation of each degradation process, and Nedd4-1 could play important role in breast cancer biology.

Free Research Field

腫瘍内科（乳癌）、エストロゲン受容体