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Research on splicing mechanism using a metal which disrupts splicing reaction

Research Project

Project/Area Number 18590556
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKobe University

Principal Investigator

LEE Myeong Jin  Kobe University, Graduate School of Medicine, Assistant professor (20273766)

Co-Investigator(Kenkyū-buntansha) NISHIO Hisahide  Kobe University, Graduate School of Medicine, Professor (80189258)
綾木 仁  神戸大学, 医学系研究科, 助教授 (80222701)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordssplicing related protein / Cd / SMN gene / ZNF265 / HOX gene / HOXB8 / BRCA1 / BRCA2 / in vitroスプライシング
Research Abstract

We investigated the effect of carcinogenic metal cadmium (Cd) on splicing machinery. As Cd induces various kinds of gene expressions including splicing-related proteins and changes activities of Zn-finger proteins by substitution of Zn, it is supposed that exposure to this metal may disrupt the splicing reaction. We also assessed the effects of Cd on the induction of homeobox genes which are associated with carcinogenesis.
1. We exposed Cd to fibroblast cells derived from an SMA type I patient, and measured the expression level of exon 7-excluded mRNA (Δ7-SMN) using RT-PCR. Exposure to 30-100μM CdCl_2 increased the level of Δ7-SMN by 2.5-fold. The result suggests that Cd may disrupt the splicing reaction of SMN gene. In addition, Cd exposure increased ZNF265 mRNA expression by 1.6-fold. As ZNF265 was reported to regulate the alternative splicing, it seems possible that the induction of ZN265 by Cd exposure affects the increase of Δ7-SMN.
2. Cd exposure did not induce splice variants of BRCA1 and BRCA2 genes in MCF-7 cells, however, 50μM Cd significantly decreased mRNA expressions of both genes. As these genes are known as tumor suppressor genes, reduced expression may be involved in the carcinogenic mechanism of Cd.
3. We assessed the effects of Cd on the expression levels of homeobox genes, which are associated with carcinogenesis. Among 6 homeobox genes examined in this study, only HOXB8 exhibited increased mRNA expression (5.4-fold) in COS-7 cells treated with 10gM CdCl_2. The levels of HOXA7, A9, C4, C9 and C10 mRNAs decreased by 0.1-0.3-fold. Silencing of HOXB8 mRNA expression using a siRNA increased HOXC9 and C10 mRNA expression levels by 6.6- and 1.9-fold, respectively. These results suggest that HOXB8 upregulation is associated with suppression of HOXC9 and C10, and that decreased expression of HOXC9 and C10 after Cd exposure is partly due to HOXB8 induction.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report

Research Products

(2 results)

All Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Cadmium exposure induces expression of the HOXB8 gene in COS-7 cells

    • Author(s)
      Kanako Nakagawa, et. al.
    • Journal Title

      Toxicology in Vitro (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cadmium exposure induces expression of the HOXB8 gene in COS-7 cells

    • Author(s)
      Kanako, Nakagawa, Myeong, Jin Lee, Naokom Sasaki, Chiyo, Hayashi, Hisahide, Nishio
    • Journal Title

      Toxicology in Vitro (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-03-31   Modified: 2016-04-21  

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