Estrogenic actions in human breast carcinoma : analyses for expression and regulation of the estrogen responsive genes
| Project/Area Number |
15590294
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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 |
Human pathology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUZUKI Takashi Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (10261629)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Breast cancer / Estrogen / Responsive gene / Nuclear receptor / Breast cancer / Estrogen / Efp / PPAR / Breast Cancer / ERR / Microarray |
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| Research Abstract |
In order to obtain a better understanding of estrogenic actions in human breast carcinomas, I have examined expression and regulation of estrogen responsive genes in breast carcinoma tissues. I first performed laser capture microdissection/microarray analyses in 20 breast carcinoma tissues. From these results, I selected following genes as possibly potent regulators of the estrogenic actions, and I further examined the biological and clinical significance of these in breast carcinomas.
1.Efp : Efp was immunolocalized in 73% of breast carcinoma tissues. Efp immunoreactivity was positively associated with estrogen receptor (ER)α and lymph node status, and was an independent prognostic factor for breast carcinoma patients. These results suggest that Efp is closely involved in a estrogen-mediated breast cancer growth.
2.ERRα : ERRα was previously identified as a gene related to ERα, and belongs to a class of nuclear orphan receptor. Significant associations were detected between ERα and ERE-containing estrogen responsive genes in breast carcinoma tissues, but the association was vanished in a part of ERE-containing estrogen responsive genes according to the ERRα-status, suggesting a possible modulation of estrogenic actions by ERRα. ERRα immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome of the patients.
3.PPARγ : PPARγ immunoreactivity was detected in 39% of breast carcinoma tissues, and was significantly associated with the status of ERα. Ligand-mediated PPARγ activation significantly inhibited estrogen-mediated ERE transactivation in MCF-7 breast carcinoma cells. in microarray analysis, inhibition of estrogen-mediated mRNA expression by PPARγ was detected in 33% of estrogen-responsive genes. These results suggest that PPARγ is also modulates estrogenic actions in ER-positive breast carcinomas.
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Report
(4 results)
Research Products
(28 results)
