| Project/Area Number |
14570114
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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 medical chemistry
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
MAEKAWA Toshio RIKEN (The Institute of Physical and Chemical Research), Lab. of Molec. Genet., Senior Scientist, 分子遺伝学研究室, 副主任研究員 (90201764)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | ATF-2 / mammary tumor / DNA chip / hypoxia / GADD45α / apoptosis / knockout mouse / BRCA1 / Maspin / 低酸素(ハイポキシア) / 転写因子 / GADD45α / アニソマイシン |
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| Research Abstract |
Transcription factor ATF-2 is a nuclear target of stress-activated protein kinases (SAPKs), which is involved in stress-induced apoptosis. Here I report that Atf-2 heterozygous mutant mice are highly prone to spontaneous formation of certain types of mammary tumours including scirrhous adenocarcinoma. The level of ATF-2 mRNA is also reduced in similar types of human breast cancers. The Atf-2-deficient mouse embryonic fibroblasts are more resistant to the hypoxia-induced apoptosis than wild-type cells, and cannot induce Gadd45α gene expression in response to hypoxia and anisomycin. The Gadd45α mRNA levels are also reduced in mammary tumors of Atf-2 heterozygous mice.
ATF-2 forms a complex with BRCA1,the most common tumour suppressor of breast cancers, and is recruited to the GADD45α promoter via two transcription factors Oct-1 and NF-I to activate the GADD45α gene transcription. Thus, AFT-2 acts as a tumor suppressor of certain types of breast cancers by inducing GADD45α transcription with BRCA1 in response to hypoxia stress.
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