Regulation of the metabolite profile by an APC gene mutation in colorectal cancer

Tomoo Yoshie, Shin Nishiumi, Yoshihiro Izumi, Aya Sakai, Jun Inoue, Takeshi Azuma, Masaru Yoshida

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

Mutation of the APC gene occurs during the early stages of colorectal cancer development. To obtain new insights into the mechanisms underlying the aberrant activation of the Wnt pathway that accompanies APC mutation, we carried out a gas chromatography-mass spectrometry-based semiquantitative metabolome analysis. In vitro experiments comparing SW480 cells expressing normal APC and truncated APC indicated that the levels of metabolites involved in the latter stages of the intracellular tricarboxylic acid cycle, including succinic acid, fumaric acid, and malic acid, were significantly higher in the SW480 cells expressing the truncated APC. In an in vivo study, we found that the levels of most amino acids were higher in the non-polyp tissues of APC min/+ mice than in the normal tissues of the control mice and the polyp tissues of APC min/+ mice. Ribitol, the levels of which were decreased in the polyp lesions of the APC min/+ mice and the SW480 cells expressing the truncated APC, reduced the growth of SW480 cells with the APC mutation, but did not affect the growth of SW480 transfectants expressing full-length APC. The level of sarcosine was found to be significantly higher in the polyp tissues of APC min/+ mice than in their non-polyp tissues and the normal tissues of the control mice, and the treatment of SW480 cells with 50 μM sarcosine resulted in a significant increase in their growth rate. These findings suggest that APC mutation causes changes in energetic metabolite pathways and that these alterations might be involved in the development of colorectal cancer.

本文言語英語
ページ(範囲)1010-1021
ページ数12
ジャーナルCancer Science
103
6
DOI
出版ステータス出版済み - 6 2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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