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Functional analysis of cyclin D1 alternative transcript b

Research Project

Project/Area Number 10670980
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAICHI CANCER CENTER

Principal Investigator

HOSOKAWA Yoshitaka  LABORATORY OF CHEMOTHERAPY, SECTION CHIEF, 化学療法部, 室長 (60229193)

Co-Investigator(Kenkyū-buntansha) SETO Masao  LABORATORY OF CHEMOTHERAPY, CHIEF, 化学療法部, 部長 (80154665)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsLymphoma / chromosome translocation / cyclin D1 / マントル細胞性リンパ腫 / モノクローナル抗体
Research Abstract

The cyclin D1/PRAD1 oncogene, a key regulator of the G1 phase progression of the cell cycle has been identified as the long-sought BCL-1 oncogene in B-cell malignancies with t(11;14)(q13;q32) translocation. Recently, a novel alternative spliced cyclin D1 transcript, called transcript [b], has been identified by ourselves. The level of the variant transcript [b] was lower than that of the originally reported cyclin D1 transcript, called transcript [a], in several human non-lymphoid cancer cell lines but the endogenous cellular expression of transcript [b] products has not yet been determined. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the transcript [b] mRNAs are well expressed in B-lymphoid cell lines with t(11;14)(q13;q32) translocation and at much lower or undetectable levels in other cells. Western blot analysis using a human cyclin D1-specific monoclonal antibody, which can recognize and distinguish the products of transcripts [a] and [b], strongly suggested that the transcript [b] protein is indeed expressed in these B-cell lines. The present study provides the first identification of the endogenous cellular expression of the cyclin D1 transcript [b] protein and strongly suggests that this alternative form of cyclin D1 may play a significant role in the molecular pathogenesis of B-lymphoid malignancies with t(11;14)(q13;q32) translocation. Further studies are warranted to study the biological function of transcript [b] and its role in cell cycle control.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Hosokawa, Y. et al.: "Cylin D1/PRAD1/BCL-1 alternative transcript[b]protein product in B-lymphoid malignancies with t(11 ; 14)(q13 ; q32) translocation"International Journal of Cancer. 81. 616-619 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Joh, T. et al.: "Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7, Hox b7 and Hox c9 expression by MLL-LTG9"Oncogene. 18. 1125-1130 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki R, et al.: "Selective usage of D-type cyclins in lymphoid malignancies"Leukemia. 13. 1335-1342 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa, Y. et al.: "Human Helios, an Ikaros-related zinc finger DNA binding protein : cDNA cloning and tissue expression pattern"Immunogenetics. 50. 106-108 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa, Y. et al.: "Human Aiolos, an Ikaros-related zinc finger DNA binding protein : cDNA cloning tissue expression pattern, and chromosomal mapping"Genomics. 61. 326-329 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa, Y. et al.: "The Ikaros gene, a central regulator of lymphoid defferentiation, fuses to the BCL6 gene as a result of t(3 ; 7)(q27 ; p12) translocation in a patient with diffuse large B-cell lymphoma"Blood. (in preww). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Joh, T., Hosokawa, Y., Suzuki, R., Takahashi, T., and Seto, M.: "Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7, Hox b7 and Hox c9 expression by MLL-LTG9 in 32Dc13 cells."Oncogene. 18. 1125-1130 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa Y, Joh T, Maeda Y, Arnold A, and Seto M.: "Cyclin D1/PRAD1/BCL-1 alternative transcript [b] protein product in B-lymphoid malignancies with t(11;14)(q13;q32) translocation."Int. J. Cancer.. 81. 616-619 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akagi, T., Tamura, A., Motegi, M., Suzuki, R., Hosokawa, Y., Nakamura, S., Morishima, Y., Seto, M., and Taniwaki, M.: "Molecular cytogenetic delineation of the breakpoint at 18q21.1 in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue."Genes Chrom. & Cancer. 24. 315-321 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akagi, T., Motegi, M., Tamura, A., Suzuki, R., Hosokawa, Y., Suzuki, H., Ota, H., Nakamura, S., Morishima, M., Taniwaki, M., Seto, M.: "A novel gene, MALT1 at 18q21, is involved in t(11;18)(q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue."Oncogene,. 18. 5785-5794 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki, H., Motegi, M., Akagi, T., Hosokawa, Y., Seto, M.: "API1-MALT1/MLT is involved in MALT lymphoma with t(11;18)(q21;a21)."Blood. 94. 3270-3271 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa Y, Maeda Y, and Seto M.: "Human Helios, an Ikaros-related zinc finger DNA binding protein: cDNA cloning and tissue expression pattern."Immunogenetics. 50. 106-108 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa Y, Maeda Y, Takahashi E, Suzuki M, and Seto M.: "Human Aiolos, an Ikaros-related zinc finger DNA binding protein: cDNA cloning, tissue expression pattern, and chromosal mapping."Genomics. 61. 326-329 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi H, Hosokawa Y, Suzuki R, Morishima Y, Nakamura S, and Seto am.: "Infrequent BCL10 mutations in B-cell non-Hodgkin's lymphomas."Jpn. J. Cancer Res.. 90. 1316-1320 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa Y, Nagai E, and Seto M.: "Truncated TSG101 transcripts in human leukemia and lymphoma cell lines."J. Cancer Res. Clin. Oncology.. 18. 79-84 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa, Y., Maeda, Y., Ichinohasama, R., Miura, I., Taniwaki, M. and Seto, M.: "The Ikaros gene, a central regulator of lymphoid differentiation, fuese to the BCL6 gene as a result of t(3;7)(q27;q12) translocation in a patient with diffuse large B-cell lymphoma."Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Motegi, M., Yonequmi, M., Suzuki, H., suzuki, R., Hosokawa, Y., Hosaka, S., Kodera, Y., Morishima, M., Nakamura, S. and Seto, M.: "API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogenous products."Am. J. Pathol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa Y, Maeda Y, and Seto M.: "Low frequency of expression of dominant negative Ikaros isoforms in human leukemia and lymophoma cell lines."Leukemia Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi H, Maeda Y, Seto M, and Hosokawa Y.: "Nucleotide insertions and deletions within the homopolymeric runs of adenines and thymidines of BCL10 cDNA in normal peripheral blood leukocytes."Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hosokawa, Y. et al.: "Cyclin D1/PRAD1/BCL-1 alternative transcript [b] protein product in B-lymphoid malignancies with t(11;14)(q13;q32) translocation"International Journal of Cancer. 81. 616-619 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Joh, T. et al.: "Establishment of an inducible expression system of chimenric MLL-LTG9 protein and inhibition of Hox α7, Hox b7 and Hox c9 expression by MLL-LTG9"Oncogene. 18. 1125-1130 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki R. et al.: "Selective usage of D-type cyclins in lymphoid malignancies"Leukemia. 13. 1335-1342 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hosokawa Y., et al.: "Human Helios, an Ikaros-related zinc finger DNA binding protein : cDNA cloning and tissue expression pattern"Immunogenetics. 50. 106-108 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hosokawa Y., et al.: "Human Aiolos, an Ikaros-related zinc finger DNA binding protein : cDNA cloning tissue expression pattern and chromosomal mapping"Genomics. 61. 326-329 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hosokawa Y. et al.: "The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma"Blood in press. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hosokawa,Y.et al.,: "Cyclin D1/PRAD1/BCL-1 alternative transcript[b]protein product in B-lymphoid malignancies with t(11:14)(q13;q32)translocation." International Journal of Cancer. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hosokawa,Y.et al.,: "A small deletion in the 3'-untranslated region of cyclin D1/PRAD1/BCL-1 oncogene in a patient with chronic lymphocytic leukemia" International Journal of Cancer. 76. 791-796 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hosokawa,Y.et al.,: "Molecular Mechanism of Overexpression of Cyclin D1/PRAD1 in Human Tumor Cell Lines:Analysis of Allele-specific Expression." Gene Chromosome Cancer. 22. 66-71 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hosokawa,Y.et al.,: "Human Cyclin D1(PRAD1)Alternative Transcript b:Full-length cDNA CloningExpression in Breast Cancers." Cancer Letters. 113. 123-130 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Joh,T.et al.,: "Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7,Hox b7,and Hox c9 expression by MLL-LTG9 in 32Dcl3 cells" Oncogene.18. 1125-1130 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akagi,T.et al.,: "Molecular Cytogenetic Delineation of the Break point at 18q21.1 in low-Grade B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue." Gene Chromosome Cancer.(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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