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Identification and functional analysis of novel oncogenes involved in the breast cancer genesis and promotion

Research Project

Project/Area Number 18591825
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionWaseda University (2007)
The University of Tokyo (2006)

Principal Investigator

SEMBA Kentaro  Waseda University, Dept. of Life Science and Medical Bioscience, professor (70206663)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsCancer / gene amplification / ErbB2 / proteome / signal transduction
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (22 results)

All 2008 2007 2006 Other

All Journal Article (11 results) (of which Peer Reviewed: 6 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] N0TCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells.2008

    • Author(s)
      Yamaguchi, N.
    • Journal Title

      Cancer Res 68

      Pages: 1881-1888

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] FoxAl as a lineage-specific oncogene in luminal type breast cancer.2008

    • Author(s)
      Yamaguchi, N.
    • Journal Title

      Biochem Biophys Res Commun 365

      Pages: 711-717

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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.
    • Journal Title

      Cancer Res 68

      Pages: 1881-1888

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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.
    • Journal Title

      Biochem Biophys Res Commun 365

      Pages: 711-717

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] NOTCH3 Signaling Pathway plays Crucial Roles in Proliferation of ErbB2-negative Human Breast Cancer Cells.2008

    • Author(s)
      Yamaguchi, N., et. al.
    • Journal Title

      Cancer Res 68

      Pages: 1881-1888

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FoxA1 as a lineage-specific oncogene in luminal type breast cancer.2008

    • Author(s)
      Yamaguchi, N., et. al.
    • Journal Title

      Biochem Biophys Res Commun 365

      Pages: 711-717

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast cancers.2007

    • Author(s)
      Ito, E., et al.
    • Journal Title

      FEBS Lett 581

      Pages: 3909-3914

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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.
    • Journal Title

      FEBS Lett 581

      Pages: 3909-3914

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast cancers.2007

    • Author(s)
      Ito, E., et. al.
    • Journal Title

      FEBS Lett 581

      Pages: 3909-3914

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AYUMS : an algorithm for completely automatic quantitation based on LC-MS/MS proteome data and its application to the analysis of signal transduction.2007

    • Author(s)
      Saito A, Nagasaki M, Oyama M, Kozuka-Hata H, Semba K, Sugano S, Yamamoto T, Miyano S
    • Journal Title

      BMC Bioinformatics 8

      Pages: 15-15

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Diversity of translation start sites may define increased complexity of the human short ORFeome.

    • Author(s)
      Oyama M, Kozuka-Hata H, Suzuki Y, Semba K, Yamamoto T, Sugano S.
    • Journal Title

      Mol. Cell. Proteomics (in press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] Characterization of breast cancer cells with constitutively activated NFκB2007

    • Author(s)
      山口憲孝
    • Organizer
      BMB2007
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Characterization of breast cancer cells with constitutively activated NFκB2007

    • Author(s)
      Yamaguchi N.
    • Organizer
      BMB2007
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Characterization of breast cancer cells with constitutively activated NFκB2007

    • Author(s)
      山口憲孝
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-10-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Characterization of breast cancer cells with constitutively activated NFκB2007

    • Author(s)
      Yamaguchi N
    • Organizer
      66^<th> Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Characterization of breast cancer cells with constitutive activation of NFκB2007

    • Author(s)
      Yamaguchi N, et. al.
    • Organizer
      66th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Characterization of breast cancer cells with constitutive activation of NFκB2007

    • Author(s)
      Yamaguchi N, et. al.
    • Organizer
      BMB2007 Biochemistry and Molecular Biology
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 乳癌における新規遺伝子増幅部位の同定2006

    • Author(s)
      仙波憲太郎
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of novel gene amplification units in breast cancer2006

    • Author(s)
      Semba K
    • Organizer
      65^<th> Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 乳癌細胞におけるNotch3の遺伝子増幅による増殖促進作用2006

    • Author(s)
      山口憲孝
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Amplification of NOTCH3 gene causes breast cancer cell proliferation2006

    • Author(s)
      Yamaguchi N
    • Organizer
      65^<th> Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.biomed.sci.waseda.ac.jp/

    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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