| Project/Area Number |
14370362
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nagoya City University |
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Principal Investigator |
IWASE Hirotaka Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (40211065)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Hiroko Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究科, 講師 (70332947)
遠山 竜也 名古屋市立大学, 大学院・医学研究科, 助手 (30315882)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | breast cancer / hormone related gene / cofactor / AIB 1 / NCoR1 / HDAC6 / ATBF1-A / IGFBP4 / マイクロダイセクション / エクトロゲンレセプター / エストロゲンレセプター / cDNAカスタムアレイ |
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| Research Abstract |
The assessment of the estrogen receptor (ER)α and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. However, the substantial roles of ERβ and co-factors in the development and progression of breast cancer remain to be elucidated.
To evaluate the clinical significance of these factors in the response to endocrine therapy, we investigated the expressions of ERα/β, PgR, AIB 1 and NcoR1 in primary breast cancer tissues using immunohistochemistry (IHC) and/or quantitative real-time reverse transcription-PCR.
An IHC method for quantifying ERa and PR in breast tumors was described, and shown to correlate well with the relative responsiveness to endocrine therapy. Higher expression of ERβ in breast tumors correlated with better prognosis of breast cancer patients, and this was shown using both IHC and real-time PCR methodologies. The significance of altered expression of an ERβ variant, ERβcx was unclear. Since AIB 1 expression in increased with breast cancer and correlates with ER activity, mRNA and protein levels of AIB 1 were measured and no correlation between ERα and AIB 1 mRNA was found. However, patients with breast tumors that stained positively for nuclear AIB 1 expression tended to respond to hormone therapy as compared to patients with breast tumors that did not show nuclear staining of AIB 1. Evidence was also presented suggesting that NCOR1 mRNA expression is higher in small, ERα-positive tumors, and those patients with higher expression exhibited better survival and responsiveness to tamoxifen.
ATBF1-A is a tumor suppress gene located in 16q22-24 and also have a prognostic factor in breast cancer. ATBF1-A expression might have the ability of predictive factor of endocrine therapy in breast cancer.
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