Analysis of acquired aromatase-resistance mechanisms in breast cancer
Project/Area Number |
15K10082
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General surgery
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Research Institution | Research Institute for Clinical Oncology, Saitama Cancer Center |
Principal Investigator |
Yamaguchi Yuri 埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 研究員 (80166628)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 乳癌 / ホルモン療法耐性 / エストロゲン / アロマターゼ / miRNA / HERファミリー / アロマターゼ阻害剤 / AI耐性 / 微小環境 / 癌幹細胞 |
Outline of Final Research Achievements |
To investigate the mechanisms of resistance to hormonal therapy using aromatase inhibitor in postmenopausal breast cancer, we established several estrogen-deprivation-resistant cell lines from xenograft of estrogen receptor-positive human MCF-7 cells transplanted into ovariectomized SCID mice by reflecting clinical microenvironment of estrogen-depleted therapy. Several AI cell lines were isolated from each palpable tumor detected at more than 150 days after transplantation. Most of these cell lines overexpressed ER and some lost ER expression. They showed different expressions of breast cancer stem cell markers and sensitivities to signal cascade inhibitors, suggesting that AI resistant mechanisms might be different for each case.
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Academic Significance and Societal Importance of the Research Achievements |
乳癌は女性罹患率第一位であり、現在も増加傾向にある。乳癌の3分の2はエストロゲン受容体(ER)陽性でホルモン療法が有効であるが、その3分の1で治療耐性を獲得し、再発となる症例が少なくない。本研究は閉経後乳癌におけるアロマターゼ阻害剤(AI)によるホルモン療法に注目し、その耐性機序を解明するため、卵巣を除去した免疫不全SICDマウスに乳癌細胞を移植し、生体内に近い環境下でin vivoでモデル細胞株を樹立して解析した。耐性機序は一様ではないことが判明した。個々の症例について耐性機序を診断することは多様化して来ている次治療薬の選択に重要である。
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Report
(5 results)
Research Products
(30 results)
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[Journal Article] Single CpG site methylation controls estrogen receptor gene transcription and correlates with hormone therapy resistance2017
Author(s)
Tsuboi K, Nagatomo T, Gohno T, Higuchi T, Sasaki S, Fujiki N, Kurosumi M, Takei, H, Yamaguchi Y, Niwa T, Hayashi SI
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Journal Title
J Steroid Biochem Mol Biol
Volume: 171
Pages: 209-217
DOI
Related Report
Peer Reviewed
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[Journal Article] Prognostic significance of immunohistochemical expression of the ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) in postmenopausal women with invasive breast cancer2016
Author(s)
Kurozumi S, Yamaguchi Y, Hayashi S, Hiyoshi H, Suda T, Matsumoto H, Takei H, Horiguchi J, Oyama T, Takeyoshi I, Kurosumi M
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Journal Title
Cancer Med
Volume: 5(8)
Issue: 8
Pages: 1873-1882
DOI
Related Report
Peer Reviewed / Open Access
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