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STUDIES ON MECHANISM OF AUTOCRINE GROWTH OF A HUMAN SALIVARY GLAND ADENOCARCINOMA BY EPIDERMAL GROWTH FACTOR

Research Project

Project/Area Number 03454435
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionIWATA MEDICAL UNIVERSITY

Principal Investigator

OTA Minoru  Iwata Medical University School of Dentistry Department of Biochemistry Professor, 歯学部, 教授 (70048255)

Co-Investigator(Kenkyū-buntansha) NAGAI Masazumi  ibib. Assistant, 歯学部, 助手 (00217960)
KYAKUMOTO Seiko  ibib. Assistant, 歯学部, 助手 (90118274)
KUROKAWA Riki  ibib. Assistant, 歯学部, 助手 (70170107)
NEMOTO Takayuki  ibib. Assistant, 歯学部, 講師 (90164665)
SATO Nobuko  Iwata Medical University School of Dentistry Department of Biochemistry Instruct, 歯学部, 助教授 (00048399)
根本 優子  岩手医科大学, 歯学部・歯科放射線学講座, 助手 (10164667)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsEGF / EGF-receptor / submandibular gland / c-erbB2 / autocrine growth / adenocarcinoma / 腺癌細胞 / 顎下腺細胞株 / チロシンリン酸化 / ヒト顎下腺 / ヒト顎下腺細胞株 / 上皮成長因子 / 上皮成長因子レセプタ-
Research Abstract

The human salivary gland adenocarcinoma cell line HSG proliferates autonomously, with the proliferation mediated by an autocrine growth factor, a Mr.46K epidrmal growth factor(EGF)-like molecule. In this project, the mechanism of autocrine growth of HSG by EGF-like molecule was investigated. Firstly, the expression of the intuitive candidates for the receptor, EGF receptor (EGF-R) and c-erbB2 protooncogene product, p185^<erbB2>, which closely resembles EGF-R and seems also to be a cell surface receptor, was examined. Immunoprecipitation and immunoblotting analyzes using the antibody specific to each protein revealed the expression of both EGF-R and p185^<erbB2> in HSG cells. Northern blotting analyzes also revealed the expression of 5.6 kb EGF-R mRNA and 4.6 kb c-erbB2 mRNA.The co-expression of EGF-R and p185^<erbB2> was also confirmed by immunohistochemical analyzes. When EGF-like molecule was added to the HSG cell cultures, only 170K EGF-R was autophosphorylated, and p185^<erbB2> was not. These result suggested that, although both EGF-R and p185^<erbB2> are co-expressed in HSG cells, the EGF-R is the genuine receptor for the EGF-like molecule. However, there is a possibility that p185^<erbB2> is involved in the signal transduction system. This was examined by using specific antibodies to hEGF-R, p185^<erbB2>, and EGF to inhibit the functions of these molecules. Addition of these three antibodies to the cultures inhibited the growth of HSG cells. Particularly, the effect of the anti-p185^<erbB2> antibody was the strongest in three antibodies. Moreover, the antibodies to EGF-R and p185^<erbB2> caused morphological changes such as disturbances of the plasma membrane, and some cell death. Thus, p185^<erbB2> expressed in EGF as well as EGF-R has an important function in the signal transduction of HSG cell growth.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Kurokawa,R.: "Autocrine growth of a human salivary gland adenocarcinoma cell line(HSG)." Dentistry in Japan. 28. 63-70 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nemoto,T.: "Association of the 90 kDa heat shock protein does not affect the ligandbinding ability of androgen receptor." J.steroid Biochem.Mol.Biol.42,(8). 803-812 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tamura,K.: "Characterization of the mineralocorticoid receptor in rat submandibular gland." Steroid Biochem.(Life Sci.Adv.). 11. 13-21 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nemoto,T.: "Dual roles of 90 kDa heat shock protein in the function of the miner alocorticoid receptor." J.Biochem.113,(6). 769-775 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato,N.: "cAMP-dependent phosphorylation of nuclear proteins in mouse subman dibular gland following testosterone administration." Biochem.Mol.Biol.Int.30,(1). 131-138 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kyakumoto,S.: "Co-expression of EGF receptor and c-erbB-2 proto-oncogene product in human salivary gland adenocarcinoma cell line HSG:inplication of these receptors for HSG cell autocrine growth" Archives of Oral Biology.(in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 客本斉子: "ヒト顎下腺由来腺癌細胞株(HSG)におけるレチノイン酸レセプターとレチノイン酸レスポンスエレメントとの結合" 岩手医科大学歯学雑誌. 19,(1)(in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kurokawa, R., Kyakumoto, S.and Ota, M.: "Autocrine growth of a human salivary gland adenocarcinoma cell line (IISG)." Dentistry in Japan. 28. 63-70 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nemoto, T., Ohara-Nemoto, Y.and Ota, M.: "Association of the 90-kDa heat shock protein does not affect the ligandbinding ability of androgen receptor." J.steroid Biochem.Mol.Biol.42, (8). 803-812 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tamura, K., Nemoto, T.and Ota, M.: "Characterization of the mineralocorticoid receptor in rat submandibular gland." Steroid Biochem. (Life Sci. Adv.). 11. 13-21 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nemoto, T., Ohara-Nemoto, Y., Sato, N.and Ota, M.: "Dual roles of 90-kDa heat shock protein in the function of the mineralocorticoid receptor." J.Biochem.113, (6). 769-775 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato, N., Ohara-Nemoto, Y., Sawano, K.and Ota, M.: "cAMP-dependent phosphorylation of nuclear proteins in mouse submandibular gland following testosterone administration." Biochem.Mol.Biol.Int.30, (1). 131-138 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kyakumoto, S., Kurokawa, R., Hoshino, M.and Ota, M.: "Co-expression of EGF receptor and c-erbB-2 proto oncogene product in human salivary gland adenocarcinoma cell line HSG : inplication of these receptors for HSG cell autocrine growth." Archives of Oral Biology. in press. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kurokawa,R.: "Autocrine growth of a human salivary gland adenocarcinoma cell line(HSG)." Dentistry in Japan. 28. 63-70 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ncmoto,T.: "Association of the 90 kDa heat shock protein does not affect the ligandbinding ability of androgen receptor." J.steroid Biochem.Mol.Biol.42,(8). 803-812 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tamura,K.: "Characterization of the mincralocorticoid receptor in rat submandibular gland." Steroid Biochem.(Life Sci.Adv.). 11. 13-21 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nemoto,T.: "Dual roles of 90-kDa heat shock protein in the function of the miner alocorticoid receptor." J.Biochem.113,(6). 769-775 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,N.: "cAMP dcpcndent phosphorylation of nuclear proteins in mouse subman dibular gland following testosterone administration." Biochem.Mol.Biol.Int.30,(1). 131-138 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kyakumoto,S.: "Co-cxpression of EGF receptor and c-erbB-2.proto-oncogene product in human aslivary gland aland adenocarcinoma cell line HSG :implication of these reccptors for HSG cell autocrine growth." Archives of Oral Biology.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 客本斉子: "ヒト顎下腺由来腺癌細胞株(HSG)におけるレチノイン酸レセプターとレチノイン酸レスポンスエレメントとの結合" 岩手医科大学歯学雑誌. 19,(1)(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,N.: "Effects of androgen on phosphorylation of chromosomal proteins in mouse submandibular gland." Biochem.Int.26. 843-852 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nemoto,T.: "Association of the 90-kDa heat shock protein does not affect the ligand-binding ability of androgen receptor." J.steroid Biochem.Molec.Biol.42. 803-812 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tamura,K.: "Characterization of the mineralocorticoid receptor in rat submandibular gland." Steroid Biochem.(Life Sci.Adv.). 11. 13-21 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagai,M.: "Systematic assessment of bone resorption,collagen synthesis,and clacification in chick embryonic calvaria in vitro;Effects of prostaglandin E." Bone. 93. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Riki Kurokawa: "Retinoic acid receptor in subclone of human salivary gland adenocarcinoma cell line HSG and effect of retinoic acid on cellular growth" Biochem.Biophys.Acta. 1095. 63-74 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Riki Kurokawa: "Autocrine growth of a human salivary gland adenocarcinoma cell line(HSG)" Dentistry in Japan. 28. (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yuko OharaーNemoto: "The Mr 90,000 heat shock proteinーfree androgen receptor has a high affinity for steroid,in contrast to the glucocorticoid receptor" J.Biochemistry. 109. 113-119 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nobuko Sato: "Effects of androgen on phosphorylation of chromosomal proteins in muse submandibular gland" Endocrine Research.

    • Related Report
      1991 Annual Research Report
  • [Publications] Takayuki Nemoto: "Association of the 90ーkDa heat shock protein does not affect the ligandーbinding ability of androgen receptor" J.Steroid Biochem.Mol.Biol.

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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