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1999 Fiscal Year Final Research Report Summary

Relaxation of IGF2 and KIP2 imprinting in Wilms tumours and other urogenital tumours

Research Project

Project/Area Number 10670135
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionFukui Medical University

Principal Investigator

TANIGUCHI Takanobu  Fukui Medical University, Department of Pharmacology, Associate Professor, 医学部, 助教授 (60217130)

Co-Investigator(Kenkyū-buntansha) OKADA Kenichiro  Fukui Medical University, Department of Urology, Professor, 医学部, 教授 (60026838)
Project Period (FY) 1998 – 1999
KeywordsWilms tumour / urogenital tumour / imprinting / KIP2 / IGF2
Research Abstract

Relaxation of IGF2 imprinting occurs in Wilms tumours and many other solid tumours, but the mechanism of loss of imprinting (LOI) has not yet been determined. To investigate the role of altered DNA methylation in relaxation of genomic imprinting, we have examined the pattern of DNA methylation within the complete human IGF2 gene and KIP2 gene in Wilms tumours and other urogenital tumours that have either lost or retained IGF2 imprinting. Relaxation of imprinting involves loss of the maternal imprint from the three imprinted IGF2 promoters (P2, P3 and P4) which are clustered together within a CpG island. Methylation analysis of the IGF2 CpG island showed that these three imprinted promoters were unmethylated in all Wilms tumours and in the normal kidney. However, this analysis identified a region of allele specific DNA methylation on the maternal IGF2 allele between exons 2 and 3, upstream of the imprinted IGF2 promoters, that is present in tumours with normal imprinted IGF2 expression, but lost in tumours with relaxation of imprinting. In addition a boundary of DNA methylation was found at two ALU repeat elements in intron 1 that may be involved in the imprinting process. In contrast, KIP2 gene was entirely unmethylated in all tumours and normal kidneys. From these results we postulate the existence of an upstream cis-acting methylation center in the human IGF2 that may co-ordinately control expression and imprinting from the down stream promoters. However, KIP2 gene seems to be under independent regulation of IGF2/H19 imprinting domain.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] M. J. Sullivan, T. Taniguchi, A. Jhee, et al.: "Relaxation of IGF2 imprinting in Wilms tumors associated with specific changes in IGF2 methylation"Oncogene. 18. 7527-7534 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Murata, T. Taniguchi, I. Muramatsu: "Pharmacological analysis of the novel, selective α_1-adrenoceptor antagonist, KMD-3213, and its suitability as a tritiated radioligand"British Journal of Pharmacology. 127. 19-26 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Taniguchi, R. Inagaki, S. Murata, et al.: "Microphysiometric analysis of human α_<1a>-adrenoceptor expressed in Chinese hamster ovary cells"British Journal of Pharmacology. 127. 962-968 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Nakamura, T. Taniguchi, F. Suzuki, et al.: "Evaluation of α_1-adrenoceptors in the rabbit iris : pharmacological characterization and expression of mRNA"British Journal of Pharmacology. 127. 1367-1374 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Takahashi, T. Taniguchi, S. Murata, et al.: "New α_1-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for human prostates than arteries"Journal of Urology. 161. 1350-1354 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N. Taki , T. Taniguchi, K. Okada, et al.: "Evidence for predominant mediation of α_1-adrenoceptor in the tonus of entire urethra of women"Journal of Urology. 162. 1829-1832 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.J. Sullivan: "Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation."Oncogene. 18. 7527-7534 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Murata: "Pharmacological analysis of the novel, selective αィイD21ィエD2-adrenoceptor antagonist, KMD-3213, and its suitability as a tritiated radioligand."Br. J. Pharmacol.. 127. 19-26 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Taniguchi: "Microphysiometric analysis of human αィイD21aィエD2-adrenoceptor expressed in Chinese hamster ovary cells."Br. J. Pharmacol.. 127. 962-968 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Nakamura: "Evaluation of αィイD21ィエD2-adrenoceptors in the rabbit iris: pharmacological characterization and expression of mRNA"Br. J. Pharmacol.. 127. 1367-1374 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Takahashi: "New αィイD21ィエD2-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for human prostates than arteries"J. Urology. 161. 1350-1354 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Taki: "Evidence for predominant mediation of αィイD21ィエD2-adrenoceptor in the tonus of entire urethra of women"J. Urology. 162. 1829-1832 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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