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

Alternations of Transcriptional Regulation in Oral Cancers and Analysis of Tumor Suppressive functions of p300 Transcriptional Co-activator

Research Project

Project/Area Number 13470399
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

IKEDA Masa-aki  Tokyo Med. & Dent. Univ., Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20193211)

Co-Investigator(Kenkyū-buntansha) IKEDA Yayoi  Yokohama City Univ., Medical school, Associate Professor, 医学部, 助教授 (00202903)
ADACHI Mimi  Tokyo Med. & Dent. Univ., Med. Res. Inst., Research Associate, 難治疾患研究所, 助手 (10323693)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywordsoral cancer / transcriptional coactivator / p300 / tumor suppressor gene / chromatin remodeling / E2FBP 1 / DRIL 1 / nuclear matrix / cell prolorferaction / ヒストンアセチル化酵素 / ブロモドメイン / TGFβ / ヒストアセチル化酵素
Research Abstract

The p300 acetyltransferase/transcriptional coactivator plays key roles in the regulation of cell proliferation and differentiation. Although p300 is targeted for mutations in human carcinomas, a role for p300ICBP in tumorigenesis is still remains poorly understood. In this study, we have identified p300 in two lines of human carcinoma cells (Ohshima et al. 2001, Suganuma et al. 2003). We have demonstrated that reintroduction of wild-type p300 suppressed growth of human carcinoma cells lacking normal p300, and that p300 plays an important role in the TGFJ3 signaling pathway, which is important for the negative regulation of epithelial cell growth (Suganuma et al. 2003).
To further elucidate mechanisms of tumorigenesis of oral carcinomas, we have investigated regulation of the RB tumor suppressor protein and the interaction between chromatin DNA and nuclear matrix. We have obtained several observations. (1) Cytoplasinic sequestration of cyclin D1, which is critical for RB phosphorylation, plays an important role for cell cycle exit and survival of terminally differentiated cardiomyocytes and neurons, respectively (Tamamori-Adachi et al. 2003ÅASumrejkanchanakij et al. 2003). (2) The nuclear-matrix-binding protein E2FBP1/DRIL1 is regulated by the p53 tumor suppressor (Ma et al. 2003). (3) Distinct recruitment of transcription regulatory complexes to chromatin DNA mediates activation and repression of an E2F target gene, which is regulated by the RB family proteins (Araki et al. 2003).

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (64 results)

All Other

All Publications (64 results)

  • [Publications] Ohshima, T., et al.: "A novel mutation lacking the bromodomain of the transcriptional co-activator p300 in the SiHa cervical carcinoma cell line."Biochemical and Biophysical Research Communications. 281. 569-575 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhang, Y.W., et al.: "Connexin43 suppresses proliferation of osteosarcoma U2OS cells thorugh post-transcriptional regulation of p27."Oncogene. 20. 4138-4149 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, Y., et al.: "Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary."Developmental Dynamics. 221. 443-453 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Adachi, S. et al.: "Cyclin A/cdk2 activation is involved in hypoxia-induced apoptosis in cardiomyosytes."Circulation Research. 88. 408-414 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui, M., et al.: "High Expression of HLA-A2 on an Oral Squamous Cell Carcinoma with Down-Regulated Transporter for Antigen Presentation."Biochemical and Biophysical Research Communications. 280. 1008-1014 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nonomura, Y., et al.: "Suppression of Arthritis by Forced Expression of Cyclin-Dependent Kinase Inhibitor p21Cip1 gene into the Joints."International Immunology. 13. 723-731 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suganuma, T., et al.: "Growth suppression of human carcinoma cells by reintroduction of the p300 coactivator"Proceedings of the National Academy of Science of USA. 99. 13073-13078 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gao, C.F.et al.: "P130 and its truncated form mediate p53-induced cell cycle arrest in Rb-/- Saos2 cells."Oncogene. 21. 7569-7579 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tamamori-Adachi, M., et al.: "Expression of cyclin D1 and CDK4 causes hypertrophic growth of cardiomyocites in culture : a possible implication for cardiac hypertrophy."Biochemical and Biophysical Research Communications. 296. 274-280 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, Y. et al.: "Increased expression of Mullerian-inhibiting substance correlates with inhibition of follicular growth in the developing ovary of rats treated with E2 Benzoate."Endocrinology. 143. 304-312 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 菅沼環: "p300転写コアクチベーターの変異とヒト癌細胞の細胞増殖と転写制御"口腔病学会雑誌. 69. 139-151 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 馬凱文: "p53の増殖抑制能におけるARIDファミリー蛋白質E2FBP1の関与"口腔病学会雑誌. 69. 152-161 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Araki, K., et al.: "Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter"Oncogene. 22. 7632-7641 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sumrejkanchanakij, S., et al.: "Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons"Oncogene. 22. 8723-8730 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ma, K., et al.: "E2FBP1/DRIL1,an ARID-Family transcription factor, is Regulated by p53"Molecular Cancer Research. 1. 438-444 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tamamori-Adachi, M., et al.: "Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation"Circulation Research. 92. e12-e19 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, Y., et al.: "Sexually dimorphic and estrogen-dependent expression of estrogen receptor β (ERβ) in the ventromedial hypothalamus during rat postnatal development."Endocrinology. 144. 5098-5104 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai, A., et al.: "Exposure of neonatal rats to diethylstilbestrol affects the expression of genes involved in ovarian differentiation."J.Med.Dent.Sci.. 50. 35-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sumerjkanchanakij, S: "終末分化した神経細胞におけるサイクリンD1の核移行制御"口腔病学会雑誌. 70. 131-139 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Auerkari E.I., et al.: "Expression of p16(INK4a) in tumors"Oral Oncology. 9. 241-246 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada, S., et al.: "Loss of cyclin E requirement in cell growth of an Oral Squamous Cell Carcinoma Cell Line implies deregulation of its downstream pathway"International Journal of Cancer. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 池田正明(分担): "細胞周期研究の新局面(野島博, 中山敬一, 田矢洋一編)"羊土社. 6 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 池田 正明(分担): "発生における細胞増殖制御(竹内隆, 岸本健雄編)"シュプリンガー・フェアラーク東京. 9 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohshima, T., et al.: "A novel mutation lacking the bromodomain of the transcriptional co-activator p300 in the SiHa cervical carcinoma cell line."Biochemical and Biophysical Re-search Communications. 281. 569-575 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Adachi, S., et al.: "Cyclin AIcdk2 activation is involved in hypoxia-induced apoptosis in cardiomyocytes."Circulation Research.. 88. 408-414 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui, M., et al.: "High Expression of HLA-A2 on an Oral Squamous Cell Carcinoma with Down-Regulated Transporter for Anti-gen Presentation."Biochemical and Biophysical Re-search Communications. 280. 1008-1014 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nonomura, Y, et al.: "Suppression of Arthritis by Forced Expression of Cyclin-Dependent Kinase Inhibitor p21^<Cip1> Gene into the Joints."International Immunology. 13. 723-731 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhang, Y.W., et al.: "Connexin43 suppresses proliferation of osteosarcoma U2OS cells through post-transcrip-tional regulation of p27."Oncogene. 20. 4138-4149 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, Y., et al.: "Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary."Developmental Dynamics.. 221. 443-453 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suganuma, T., et al.: "Growth suppression of human carcinoma cells by reintroduction of the p300 coactivator"Proceedings of the National Academy of Science of USA. 99. 13073-13078 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Gad, C.F., et al.: "P130 and its truncated form mediate p53-induced cell cycle arrest in Rb-/-Saos2 cells"Oncogene. 21. 7569-7579 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tamamorl-Adachi, M., et al.: "Expression of cyclin Dl and CDK4 causes hypertrophic growth of cardiomyocytes in culture: a possible implication for cardiac hypertrophy"Biochemical and Biophysical Re-search Communications. 296. 274-2880 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, Y., et al.: "Increased expression of Mullerian-in-hibiting substance correlates with inhibition of follicular growth in the developing ovary of rats treated with E2 Benzoate"Endocrinology. 143. 304-312 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Araki, K., et al.: "Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter."Oncogene. 22. 7632-7641 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sumrejkanchanakij, S., et al.: "Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons"Oncogene. 22. 8723-8730 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ma, K., et al.: "E2FBP1/DRIL1, an ARID-Family transcription factor, is Regulated by p53"Molecular Cancer Research. 1. 438-444 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tamamori-Adachi, M., et al.: "Critical role of cyclin Dl nuclear import in cardiomyocyte proliferation."Circulation Research. 92. e12-e19 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ikeda, Y., et al.: "Sexually dimorphic and estrogen-de-pendent expression of estrogen receptor β (ER β) in the ventromedial hypothalamus during rat postnatal development."Endocrinology. 144. 5098-5104 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai, A., et al.: "Exposure of neonatal rats to diethyl-stilbestrol affects the expression of genes involved in ovarian differentiation."J.Med.Dent.Sci.. 50. 35-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Auerkari E.I., et al.: "Expression of p16(INK4a) in tumors."Oral Oncology.. 9. 241-246 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada, S., et al.: "Loss of cyclin E requirement in cell growth of an Oral Squamous Cell Carcinoma Cell Line implies deregulation of its downstream pathway."International Journal of Cancer. (In press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sumrejkanchanakij, S., et al.: "Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons"Oncogene. 22. 8723-8730 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ma, K., et al.: "E2FBP1/DRIL1, an ARID-Family transcription factor, is Regulated by p53."Molecular Cancer Research. 1. 438-444 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tamamori-Adachi, M., et al.: "Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation."Circulation Research. 92. e12-e19 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikeda, Y., et al.: "Sexually dimorphic and estrogen-dependent expression of estrogen receptor β (ER β) in the ventromedial hypothalamus during rat post natal development."Endocrinology. 144. 5098-5104 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagai, A., et al.: "Neonatal rat exposure to diethylstilbestrol (DES) affects the expression of genes involved in ovarian differentiation."Journal of Medical and Dental Science. 50. 35-40 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sumrejkanchanakij, S: "終末分化した神経細胞におけるサイクリンD1の核移行制御"口腔病学会雑誌. 70. 131-139 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Araki, K., et al.: "Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter"Oncogene. 22. 7632-7641 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Auerkari E.I., et al.: "Expression of p16(INK4a) in tumors"Oral Oncology. 9. 241-246 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada, S., et al.: "Loss of cyclin E requirement in cell growth of an Oral Squamous Cell Carcinoma Cell Line implies deregulation of its downstream pathway"International Journal of Cancer. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 池田正明(分担): "細胞周期研究の新局面(野島博・中山敬一・田矢洋一編)"羊土社. 6 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 池田 正明(分担): "発生における細胞増殖制御(竹内隆・岸本健雄 編)"シュプリンガー・フェアラーク東京. 9 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suganuma, T., Kawabata, M., Ohshima, T., Ikeda, M.A.: "Growth suppression of human carcinoma cells by reintroduction of the p300 coactivator"Proceedings of the National Academy of Science of USA. 99. 13073-13078 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamamori-Adachi, M., Ito, H., Nobori, K., Hayashida, K., Kawauchi, J., Adachi, S., Ikeda.M.A., Kitajima.S.: "Expression of cyclin D1 and CDK4 causes hypertrophic growth of cardiomyocytes in culture : a possible implication for cardiac hypertrophy"Biochem. Biophys. Res. Commun.. 296. 274-280 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Gao, C.F., Ren, S., Wang, J., Zhang, S.L..Jin, F., Nakajima, T., Ikeda, M.A., Tsuchida, N: "P130 and its truncated form mediate p53-induced cell cycle arrest in Rb-/-Saos2 cells"Oncogene. 21. 7569-7579 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda, Y., Nagai A., Ikeda, M.A., Hayashi, S.: "Increased expression of Mullerian-inhibiting substance correlates with inhibition of follicular growth in the developing ovary of rats treated with E2 Benzoate"Endocrinology. 143. 304-312 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamamori-Adachi, M., Ito, H., Sumrejkanchanakij, S., Adachi, S., Hiroe, M., Shimizu, M., Kawauchi.J., Sunamori, M., Marumo, F., Kitajima.S., Ikeda, M.A.: "Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation"Circulation Research. 92. e21-e19 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagai, A., Ikeda, Y., Aso, T., Eto, K., Ikeda, M.-A.: "Neonatal rat exposure to diethylstilbestrol (DES) affects the expression of genes involved in ovarian differentiation"J. Med. Dent. Sci.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang, Y.W., Morita, I., Ikeda, M.A., Ma, K.W. Murota, S.: "Connexin43 suppresses proliferation of osteosarcoma U2OS cells through post-transcriptional regulation of p27"Oncogene. 20. 4138-4149 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda, Y., Nagai, A., Ikeda, M.A., Hayashi, S: "Neonatal estrogen exposure inhibits steroidgenesis in the developing rat ovary"Developmental Dynamics. 221. 443-453 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohshima, T., Suganuma, T., Ikeda, M.A.: "A novel mutation lacking the bromodomain of the transcriptional co-activator p300 in the SiHa cervical carcinoma cell line"Biochem. Biophys. Res. Commun.. 281. 569-575 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Adachi. S., Ito H., Tamamori-Adachi. M., Ono. Y., Nozato. T., Abe, S., Ikeda. M.A., Marumo. F., Hiroe, M.: "Cyclin A/cdk2 activation is involved in hypoxia-induced apoptosis in caidiomyocytes"Circulation Research. 88. 408-414 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsui, M., Ikeda, M. A., Akatsuka T.: "High Expression of HLA-A2 on an Oral Squamous Cell Carcinoma with Down-Regulated Transporter for Antigen Presentation"Biochem. Biophys. Res. Commun.. 280. 1008-1014 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nonomura, Y., Kosaka, H., Nasu. K., Terada, Y., Ikeda. M.A., Miyasaka, N.: "Suppression of Arthritis by Forced Expression of Cyclin-Dependent Kinase Inhibitor p21^<Cipl> Gene into the Joints"Internat. Immunol.. 13. 723-731 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi