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2000 Fiscal Year Final Research Report Summary

ANALYSIS OF THE GENE PROMOTERS OF HUMAN BONE MORPHOGENETIC PROTEINS

Research Project

Project/Area Number 11670214
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKOBE UNIVERSITY

Principal Investigator

KITAZAWA Sohei  KOBE UNIVERSITY SCHOOL OF MEDICINE, 2ND DEPARTMENT OF PATHOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (90186239)

Project Period (FY) 1999 – 2000
KeywordsBMP / gene promoter / gene transfection / gel shift assay / CpG methylation
Research Abstract

Bone morphogenetic proteins (BMPs), first identified as factors inducing heterogeneous bone and cartilaginous tissues, are now known to play important roles in organogenesis during embryonic development. The amino acids sequences of BMPs are also known to be well conserved from Drosophila to mammalian. So far, BMPs are classified into several subgroups according to their amino acids holomogy. Little is known, however, about the physiologic role and functional sharing of each BMP.In this study, we tried to characterize each BMP's functional sharing by analyzing promoter region of the each BMP gene regardless of the recent classification system based on amino acid homology. The characterization of 5'-flanking region, a promoter structure, is now mostly for the study of the regulation mechanism of gene expression of the specific target gene. By inclusive molecular cloning of the promoter area, we extended the promoter study to 're'-classify a group of genes sharing similar amino acid sequences. Furthermore, we have developed an unique and sensitive in situ hybridization system using a single-stranded DNA probes yielded by polymerase chain reaction (PCR), and used that technique to study how each BMP gene was regulated by transcriptional factors including Hox genes. During this research period, we especially characterized BMP-5 and BMP-6 gene promoters both in normal and pathologic condition as prostate cancer, and found that BMP-6 gene was epigenetically regulated by CpG methylation around the Sp1 transcriptional factor binding sites. On the other hand, BMP-5 lacks such CpG rich area, and regulated by repeated ATTA motifs recognized by Hox genes. As a rule, we performed our studies so that molecular biological assay always went together with morphological analysis. We have presented our data at various international as well as domestic meetings, and publish a lot of scientific papers for academic journals.

  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Kitazawa S et al: "Transcriptional regulation of rat Cyclin D1 gene by CpG methylation status in promoter region"J Biol Chem. 274. 28787-28793 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitazawa S et al: "In situ hybridization with polymerase chain reaction (PCR)-derived single-stranded DNA probe and S1 nuclease."Histochem Cell Biol. 111. 7-12 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kitazawa R et al: "Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene."BBA. 1445. 134-141 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kitazawa S et al: "Identification of methylated cytosine from archival formalin-fixed paraffin-embedded specimens."Lab Invest. 80. 275-276 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] Sakamoto Y et al: "Methykation of CpG loci in 5'-flanking region alters steady-state expression of adenomatous polyposis gene in colon cancer cell line."J Cell Biochem. (in press).

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      「研究成果報告書概要(和文)」より
  • [Publications] Tamada H et al: "Methylation of CpG island of human bone morphogenetic protein-6 gene promoter alters its steady-state expression in prostatic lesion."J Bone Miner Res. (in press).

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      「研究成果報告書概要(和文)」より
  • [Publications] 河野範男 他: "臨床腫瘍学(第2版)"癌と化学療法社. 2660 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kitazawa S, Kitazawa R, Maeda S: "Transeriptional regulation of rat Cyclin D1 gene by CpG methylation status in promoter region."J Biol Chem. 274. 28787-28793 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitazawa S, Kitazawa R, Maeda S: "In situ hybridization with polymerase chain reaction-derived single-stranded DNA probe and S1 unclease."Histochem Cell Biol. 111. 7-12 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitazawa R, Kitazawa S, Maeda S: "Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene."Biochemica et Biophysica Acta. 1445. 134-141 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kitazawa R, Kitazawa S, Yoon S, Kasuga M, Maeda S.: "In situ demonstration of parathyroid hormone-related protein (PTHrP) mRNA in selerosing hepatic carcinoma."Virchows Arch Int J Pathol. 435. 137-142 (1999)

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  • [Publications] Fujii H, Kitazawa R, Maeda S, Mizuno K, Kitazawa S: "Expression of platelet derived growth factor (PDGF) proteins and their receptor a. b mRNA during fracture healing in normal mouse."Histochem Cell Biol. 112. 131-138 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Zhou Y, Kato H, Shan D, Minami R, Kitazawa S, Matsuda T, Arima T, Barrett JC, Wake N: "Involvement of mutation in the DPC4 promoter in endometrial carcinoma development."Molecular Carcinogenesis. 25. 64-72 (1999)

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  • [Publications] Kohno N, Kitazawa S, Konisni M, Wakita K, Furuya Y, Kawaguchi K.: "New treatment strategy for bone metastasis from breast cancer."Breast Cancer. 6. 292-297 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimoto T, Kitazawa R, Kitazawa S, Fujii H, Maeda S, Mizuno K: "BMP-3 mRNA expression during fracture healing"Bone Joint Ligament. 12 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kohno N, Kitazawa S, Kawaguchi K: "Bisphosphonate and therapy of bone metastasis of the breast cancer"CLINICAL CALCIUM. 9. 56-62 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kohno N, Kitazawa S, Nishihara T, Wakita K: "Bisphosphonate now and the future (TOPICS) : Can breast cancer metastasis be preventable by bisphosphonate therapy?"Igakuno Ayumi. 189. 127 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yano S, Sugumoto T, Kanzawa M, Chihara K, Kitazawa R, Kitazawa S, Maeda S, Kobayashi K: "A case of secondary hyperparathyroidism showing abnormal PTH and high bone turnover : calcium sensing receptor in pathogenesis"CLINICAL CALCIUM. 9. 98-101 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kohno N, Kitazawa S, Ogata E.: "2. Malignancy associated hypercalcemia"Clinical Oncology. (2nd Edition). 1680-1690 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitazawa S, Kitazawa R, Maeda S: "Identification of methylated cytosine from archival formalin-fixed paraffin-embedded specimens."Lab Invest. 80. 275-276 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gohji K, Nomi M, Niitani Y, Kitazawa S, Fujii A, Katsuoka Y, Nakajima M: "Independent prognostic value of serum hepetocyte growth factor in baldder cancer."J Clin Oncol. 18. 2963-2971 (2000)

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  • [Publications] Yano S, Sugimoto T, Tsukamoto T, Chihara K, Kobayashi A, Kitazawa S, Maeda S, Kitazawa R: "Association of decreased calcium-sensing receptor expressino with proliferation of parathyroid cells in secondary hyperplasia."Kidney Int. 58. 1980-1986 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Uozumi M, Murao S, Kitazawa S, Amatsu M, Maeda S: "Induction of S100A4 gene expression inhibits in vivo invasiveness of human squamous cell carcinoma."Cancer Letters. 149. 135-141 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Niemhom S, Kitazawa S, Murao S, Kunachak S, Maeda S.: "Co-expression of p53 and bcl-2 may correlate to the presence of epstein-bar virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma."Cancer Letters. 160. 199-208 (2000)

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  • [Publications] Nakayama I, Murao S, Kirazawa S, Asumi A, Yamamoto M, Maeda S.: "Activation of TCL1 protein in B cell lymphomas."Pathol Int. 50. 191-199 (2000)

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  • [Publications] Inamoto S, Murao S, Yokovama M, Kitazawa S, Maeda S: "Isoproterenol-induced myocardiual injury resulting in altered S100A11 protein expression in rat."Pathol Int. 50. 480-484 (2000)

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  • [Publications] Katayama N, Murao S, Ajiki T, Kitzawa S, Onoyama H, Kuroda Y, Maeda S: "The role of S100A4 gene encoding an S100-related calcium-binding protein in human bile duct adenocarcinoma cell line : correlation of S100A4 expression and invasive growth in matrigel matrx."Int J Mol Med. 6. 539-542 (2000)

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  • [Publications] Takeuchi K, Murata K, Funaki K, Kitazawa S, Kitazawa R: "Immunohistochemical detection of parathyroid hormone-related protein in a squamous cell carcinoma arising from mature cystic teratome causing humoral hypercalcemia of malignancy."Gynec Oncol. 79. 504-507 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi K, Murata K, Funaki K, Fujita I, Hayakawa Y, Kitazawa S.: "Liposarcoma of the uterine cervix : case report."Eur J Gynaec Onclol. 21. 290-291 (2000)

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  • [Publications] Kanbara K, Ishikawa Y, Nakaya M, Nishimura R, KizakiT, Kitazawa R, Kitazawa S: "A case of squamous cell carcinoma of the small intestine"Ganno Rinsho. 46. 158-162 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yano S, Sugimoto T, Kamisawa M, Kitazawa R, Kitazawa S, Maeda S, Kobayashi K, Chihara K.: "A case of hemodyalytic patient with proliferation of parathyroid cells due to vitamin D receptor and calcium sensing receptor abnormalities."Toseki-gakkaishi. 33. 53-59 (2000)

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  • [Publications] Kitazawa S, Kitazawa R, Maeda S: "1) non-radioactive probes."Byori-to-Rinsho. 18(supp). 241-251 (2000)

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  • [Publications] Fujimoto T, Kitazawa R, Mizuno K, Maeda S, Kitazawa S: "BMP-3 mRNA expression during endochondral ossification of mouse bone tissues."Acta Histochem Cytochem.. in press. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamnada H, Kitazawa R, Gohji K, Kitazawa S: "Epigenetic regulation of human bone morphogenetic protein 6 gene expression in prostatic cancer."J Bone Miner Res. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakamoto Y, Kitazawa R, Maeda S, Kitazawa S: "Methylation of CpG loci in 5'-flanking region alters steady-state expression of adenomatous polyposis coli gene in colon cancer cell line."J Cell Biochem. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gohji K, Kitazawa S, Tamada H, Katsuoka Y, Nakajima M: "Expression of endothelin receptor-A associated with prostate cancer progression."J Urol. (in press). (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kitazawa R, Kitazawa S.: "Transcriptional regulation mechanism of mouse RANK ligand (RANKL) gene."J Biol Chem. (in press). (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Ueno H, Yoneda R, Ogawa W, Yoon S, Kitazawa S, Kitazawa R, Kasuga M: "Bilateral interstitial pneumonic shadows caused by perivascular fibrosis and extramedullary megakaryopoiesisof the lung in a case of advanced agnogemic meyloid metaplasia and myelofibrosis."Acta Haematol. (in press). (2001)

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  • [Publications] Onishi T, Yamakawa K, Franco OE, Kawamura J, Watanabe M, Shiraishi T, Kitazawa S: "Mitogen-activated protein kinase pathway is involved in α6 integrin gene expression in androgen-independent prostate cancer cells : role of proximal Spl consensus sequence."BBA. (in press). (2001)

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Published: 2002-03-26  

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