• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

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
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsBMP / gene promoter / gene transfection / gel shift assay / CpG methylation / gelshift assay / gelshift Assay
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.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 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
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitazawa R et al: "Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene."BBA. 1445. 134-141 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitazawa S et al: "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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 河野範男 他: "臨床腫瘍学(第2版)"癌と化学療法社. 2660 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitazawa R, Kitazawa S, Maeda S: "Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene."Biochemica et Biophysica Acta. 1445. 134-141 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kohno N, Kitazawa S, Kawaguchi K: "Bisphosphonate and therapy of bone metastasis of the breast cancer"CLINICAL CALCIUM. 9. 56-62 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitazawa S, Kitazawa R, Maeda S: "1) non-radioactive probes."Byori-to-Rinsho. 18(supp). 241-251 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitazawa R, Kitazawa S.: "Transcriptional regulation mechanism of mouse RANK ligand (RANKL) gene."J Biol Chem. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitazawa S et al: "Identification of methylated cytosine from archival formalin-fixed paraffin-embedded specimens."Lab Invest. 80・2. 275-276 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yano S et al: "Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hypreparathyoidism."Kidney Int. 58・11. 1980-1986 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi K et al: "Immunohistochemical detection of PTHrP in a squamous cell carcinoma arising from mature cystic teratoma causinh humoral hypercalcemia of malignancy."Gynecol Oncol. 79・3. 504-507 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北澤荘平 他: "免疫組織化学とin situ hybridizationのすべて:非放射性プローブ."病理と臨床. 18・臨時増刊号. 245-251 (2000)

    • Related Report
      2000 Annual Research Report
  • [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).

    • Related Report
      2000 Annual Research Report
  • [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).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitazawa R et al: "Promoter structure of mouse RANKL/TRANCE/OPGL/ODFgene"Biochemica et Biophysica Acta. 1445・1. 134-141 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitazawa R et al: "In situ demonstration of parathyroid hormone-related protein(PTHrP)mRNA in sclerosing hepatic carcinoma"Virchows Arch Int J Pathol. 435・2. 137-142 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitazawa S et al: "Transcriptional regulation of rat Cyclin D1 gene by CpG methylation status in promoter region"J Biol Chem. 274・40. 28787-28793 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitazawa S et al: "In situ hybridization with polymerase chain reaction-derived single-stranded DNA probe and S1 unclease"Histochem Cell Biol. 111・1. 7-12 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujii H et al: "Expression of platelet derived growth factor(PDGF)proteins and their receptor a,b mRNA during fracture healing in normal mouse"Histochem Cell Biol. 112・2. 131-138 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitazawa S et al: "Identification of methylated cytosine from archival formalin-fixed paraffin-embedded specimens"Lab Invest. (in press). (2000)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi