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Bone morphognetic proteins (BMPs) and BMP receptor expression in breast cancer cells and their significance in bone metastases

Research Project

Project/Area Number 10671050
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

TAKAHASHI Shunji  Japanese Found. for Cancer Res., Cancer Chemotherapy Center, Researcher, 癌化学療法センター臨床部, 研究員 (90221358)

Co-Investigator(Kenkyū-buntansha) OGATA Etsuro  Japanese Found. for Cancer Res., Cancer Hospital, Director, 癌研究所, 部長 (70013761)
ITO Yoshinori  Japanese Found. for Cancer Res., Cancer Chemotherapy Center, Researcher, 癌化学療法センター臨床部, 研究員 (00261131)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Keywordsbreast cancer / bone mophogenetic protein / bone metastasis / osteoblast / bone formation / estrogen receptor / bone resorption / 骨転位 / bone morphogenetic proteins / 破骨細胞
Research Abstract

Breast cancer often cause osteoblastic bone metastasis, but its mechanisms are not elucidated. We investigated gene expression of BMPs and BMP receptors in breast cancer cells and the effect of BMP on those cells. RT-PCR analysis revealed that all human breast cancer tissue samples expressed several of examined BMP (2-7) mRNAs.. Immunoblot of conditioned media of those cell lines detected secretion of BMP-2. Correlation of BMP-6 mRNA expression in breast cancer samples and presense of bone metastases was found. All breast cancer samples examined expressed BMP-receptor type 1 and type 2 mRNAs. BMP-2 and BMP-4 inhibited growth of estrogen receptor (ER)-positive cells lines (MCF-7, ZR-75-1, T47D) at 10-200 ng/ml, and estradiol antagonized the inhibitory effect of BMP. BMP had no effect on ER activity in MCF-7 or T47D cells, but BMP inhibited phosphorylation of signal transducers and activators of transcription (stat)-3. These observations suggest that BMPs might have regulatory role in breast cancer cell growth and participate in interaction of can cer cell and bone microenvironment in bone metastasis.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] M.Koizumi, Takahashi, S., et al.: "Bone metabolic markers in bone metastasis of breast cancer"Int.J.Clin.Oncol. 4. 331-337 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Koizumi, Takahashi, S., et al.: "Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer"Clinical Nuclear Medicine. 14. 15-20 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 高橋俊二, 吉田敦行他: "高副甲状腺ホルモン関連蛋白(PT-HrP)血症患者における血中サイトカインレベルの上昇"臨床内分泌代謝Update : Proceeding. 1. 40-43 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Koizumi, Takahashi, S., et al.: "Bone Metabolic Markers and metastatic bone tumors"Res.Adv.In Cancer. 1. 33-46 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiyama K., Takahashi, S., et al.: "Irinotecan Hydrochloride for Recurrent and Refractory Non-Hodgkin's Lymphoma : Single Institution Experience"Cancer. 94. 594-600 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koizumi M, Takahashi S, Ogata E: "Bone metabolic markers in bisphosphonate therapy for skeletal metastases in patients with breast cancer"Breast Cancer. 10. 21-27 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 高橋俊二他: "8.癌に伴う骨疾患"カルシウムと骨(朝倉書店). 390-398 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Koizumi, S. Takahashi, and E. Ogata: "Bone metabolic markers in bone metastasis of breast cancer"Int. J. Clin. Oncol. 4. 331-337 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mitsuru Koizumi, Seiichi Matsumoto, Shunji Takahashi, Takashi Yamashita, and Etsuro Ogata: "Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer"Clinical Nuclear Medicine. 14(1). 15-20 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Taniguchi, N. Chikatsu, S. Takahashi, A. Fujita, K. Uchimaru, S. Asano, T. Fujita and T. Motokura: "Expression of p16INK4A and p14ARF in hematological malignancies"Leukemia. 13. 1760-1769 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mitsuru Koizumi, Shunji Takahashi, and Etsuro Ogata: "Bone Metabolic Markers and metastatic bone tumors"Res. Adv. In Cancer. 1. 33-46 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito. Y., Aiba, K., Horikoshi, N., Saotome, T., Irie, T., Sugiyama, K., Nakane, M., Hashimoto, D., Yoshida, N., Mizunuma, N., Takahashi, S., and Tanigawa, Y.: "Dose-finding phase I study of simulataneous weekly infusion with doxorubicin and docetaxel in patients with advanced breast cancer"Int. J. Clin. Oncol. 6. 242-247 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki Sugiyama, Ken Omachi, Keiichi Fujiwara, Takeshi Saotome, Nobuyuki Mizunuma, Shunji Takahashi, Yoshinori Ito, Keisuke Aiba, and Noboru Horikoshi: "Irinotecan Hydrochloride for Recurrent and Refractory Non-Hodgkin's Lymphoma : Single Institution Experience"Cancer. 94(3). 594-600 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koizumi M, Takahashi S, Ogata E: "Bone metabolic markers in bisphosphonate therapy for skeletal metastases in patients with breast cancer"Breast Cancer. 10. 21-7 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Koizumi, Thkahashi.S., et al.: "Bone Metabolic Markers and metastatic bone tumors"Res.Adv.In Cancer. 1. 33-46 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama K., Takahashi.S., et al.: "Irinotecan Hydrochloride for Recurrent and Refractory Non-Hodgkin's Lym-phoma : Single Institution Experience"Cancer. 94. 594-600 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋俊二: "カルシウムと骨 8.癌に伴う骨疾患"朝倉書店. 390-398 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi,S.,Nagamine,T.,Ito.Y. et al.: "Bone mophogenetic proteins (BMPs) expression and their role as autocrine/paracrine inhibitory factor in breast cancer cells."Journal of Bone and Mineral Metabolism. 12. S312 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aruga,A.Takahashi,S.,Ogata,E et al..: "Usefullness of Bone Metabolic Markers in the Diagnosis and Follow up of Bone Metastasis from Lung Cancer."British J.of Cancer. 76. 760-764 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Koizumi,Takahashi,S., et al.: "Bone metabolic markers in bone metastasis of breast cancer."Int.J.Clin.Oncol. 4. 331-337 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Koizumi,Takahashi,S., et al.: "Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer."Clinical Nuclear Medicine. 14. 15-20 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋俊二,吉田敦行 他: "高副甲状腺ホルモン関連蛋白(PTHrP)血症患者における血中サイトカインレベルの上昇"臨床内分泌代謝Update:Proceeding. 1. 40-43 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋俊二 他: "カルシウムと骨8.癌に伴う骨疾患"朝倉書店(in press). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi S.,Goldring S.et al.: "Downregulation of Calcitonin Receptor mRNA Expression by Calcitonin during Human Osteoclast-like Cell Differentiation"Journal of Clinical Investigation. 95. 167-171 (1995)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi S.,Reddy S.V.et al.: "Development and Characterization of a Human Marrow Stromal Cell Line That Enhances Osteoclast-like Cell Formation"Endocrinology. 136. 1441-1449 (1995)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aruga A.,Takahashi S.,Ogata E.et al.: "Usefullnes of Bone Metabolic Markers in the Diagnosis and Follow up of Bone Metastasis from Lung Cancer"British J.of Cancer. 76. 760-764 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi S.,Nagamine T.,Ito Y.et al.: "Bone mophogenetic proteins (BMPs) expression and their role as autocrine/paracrine inhibitory factor in breast cancer cells"Journal of Bone and Mineral Metabolism. 12. S312 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Koizumi,Takahashi S.et al.: "Bone metabolic markers in bone metastasis of breast cancer"Int.J.Clin.Oncol.. 4. 331-337 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Koizumi,Takahashi S.et al.: "Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer"Clinical Nuclear Medicine. 14. 15 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi,S., Reddy,S.V.et al.: "Cloning and Identification of Annexin II as an Autocrine/Paracrine Factor that Increase Osteoclast Formation and Bone Resorption." Journal of Biological Chemistry. 269. 28696-28701 (1994)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takahashi,S., Goldring,S.et al.: "Downregulation of Calcitonin Receptor mRNA Expression by Calcitonin during Human Osteoclast-like Cell Differentiation." Journal of Clinical Investstigation. 95. 167-171 (1995)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takahashi,S., Reddy,S.V.et al.: "Development and Characterization of a Human Marrow Stromal Cell Line That Enhances Osteoclast-like Cell Formation." Endocrinology. 136. 1441-1449 (1995)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koizumi,M., Takahashi,S., Ogata,E, et al.: "Bone metabolic markers in bone metastasis." Journal of Cancer Research and Clinical Oncology. 121. 542-548 (1995)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aruga,A., Takahashi,S., Ogata,E et al.: "Usefullnes of Bone Metabolic Markers in the Diagnosis and Follow up of Bone Metastasis from Lung Cancer." British J.of Cancer. 76. 760-764 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takahashi,S., Nagamine,T., Ito,Y.et al.: "Bone mophogenetic proteins(BMPs)expression and their role as autocrine/paracrine inhibitory factor in breast cancer cells." Journal of Bone and Mineral Metabolism. 12. S312 (1997)

    • Related Report
      1998 Annual Research Report

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

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