2007 Fiscal Year Final Research Report Summary
Identification and functional analysis of novel oncogenes involved in the breast cancer genesis and promotion
| Project/Area Number |
18591825
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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 |
Obstetrics and gynecology
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| Research Institution | Waseda University (2007)
The University of Tokyo (2006) |
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Principal Investigator |
SEMBA Kentaro Waseda University, Dept. of Life Science and Medical Bioscience, professor (70206663)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Cancer / gene amplification / ErbB2 / proteome / signal transduction |
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| Research Abstract |
The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells.
Almost 20% of cancer cells show constitutive NF-кB activity, which induce expression of several genes involved in tumor growth, metastasis and angiogenesis, however, the mechanism of the constitutive activation is unclear. To answer this question, we first evaluated basal NF-кB activities of 125 human cancer cell lines from various tissues with electorophoretic mobility shift assays. We are analyzing the mechanism using the cell lines showing high NF-кB activity.
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[Journal Article] NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells.2008
Author(s)
Yamaguchi, N., Oyama, T., Ito, E., Satoh, H., Azuma, S., Hayashi, M., Shimizu, K., Honma, R., Yanagisawa, Y., Nishikawa, A., Kawamura, M., Imai, J., Ohwada, S., Tatsuta, K., Inoue, J., Semba, K., Watanabe, S.
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Journal Title
Cancer Res 68
Pages: 1881-1888
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] FoxA1 as a lineage-specific oncogene in luminal type breast cancer.2008
Author(s)
Yamaguchi, N., Ito, E., Azuma, S., Honma, R., Yanagisawa, Y., Nishikawa, A., Kawamura, M., Imai, J., Tatsuta, K., Inoue, J., Semba, K., Watanabe, S.
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Journal Title
Biochem Biophys Res Commun 365
Pages: 711-717
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast cancers.2007
Author(s)
Ito, E., Honma, R., Yanagisawa, Y., Imai, J., Azuma, S., Oyama, T., Ohwada, S., Akiyama, T., Nomura, N., Inoue, J., Watanabe, S., Semba, K.
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Journal Title
FEBS Lett 581
Pages: 3909-3914
Description
「研究成果報告書概要(欧文)」より
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