2000 Fiscal Year Final Research Report Summary
Analysis of the Estrogen Receptor α cofactors with reference to Hormone Dependency of Breast Cancer
| Project/Area Number |
11671176
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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, Medical School, Associate Professor, 医学部, 助教授 (40211065)
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| Co-Investigator(Kenkyū-buntansha) |
TOYAMA Tatsuya Nagoya City University, Medical School, Research Associate, 医学部, 助手 (30315882)
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| Project Period (FY) |
1999 – 2000
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| Keywords | estrogen receptor α / cofactors / AIBI1 / endocrine therapy / breast cancer |
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| Research Abstract |
1. Transcriptional regulation of the estrogen receptor α(ERα) in breast cancer cell lines
We analyzed the transcriptional activity of the various kinds ERα cofactors, such as SRC-1, AIB1, PCAF, and CARM1 using TATA luciferase assay in the transformed COS7 cells. The ER α transcriptional activity of AIB1 was stronger than those of SRC-1, PCAF, and CARM1. AIB1 is a member of the SRC-1 family nuclear receptor coactivators, which interact with steroid hormone receptors to enhance ligand-dependent manner.
2. Gene amplification of AIB1 in breast cancer
We analyzed 124 primary breast cancer DNAs digested with EcoRI and immobilized on Southern blotting membranes with a 1.27-kb cDNA probe. Amplification was observed in two of 124(1.6%)breast tumors. Amplification level of case 1 was 3-fold. Hybridization band of case 2 was upper-shifted and its amplification level was 5-fold. This amplification was qite rare and was thought to be unimportant for the hormonal development of breast cancer.
3. AIB1 ov
… More
erexpression in breast cancer
We performed immunohistochemical detection of AIB1 protein in 115 cases with breast cancer. The positive staining was showed in the nucleus, cytoplasm and both of them. When the nuclear staining was evaluate as positive, the positive rate was 16%(18/115). The positivity of AIB1 was correlated with ER α status(P=0.021). In the patents treated by endocrine therapy, 4 of 5 patient with positive AIB1 and positive ER were responsive for endocrine therapy, whereas only 4 of 16 patients with negative AIB1 and positive ER were responsive(P=0.047). This means that the nuclear expression of AIB1 was thought to be predictive factors for endocrine therapy in breast cancer.
4. Clinical value of the wild-type ER β expression in breast cancer.
ER β positive staining was seen in 52(59%)of 88 breast cancers. ER β staining was correlated with ER α status(P=0.02). ER β positive cases showed a better prognosis than negative cases in disease -free survival rate(Logrank test : P=0.017). Our data demonstrated the possibility that the wild-type ERβ protein expression could be used as a good prognostic indicator for breast cancer. Less
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