Cathepsin H regulated by the thyroid hormone receptors associate with tumor invasion in human hepatoma cells

S. M. Wu, Y. H. Huang, C. T. Yeh, M. M. Tsai, C. H. Liao, Wan Li Cheng, W. J. Chen, K. H. Lin

研究成果: 雜誌貢獻文章同行評審

32 引文 斯高帕斯(Scopus)

摘要

Thyroid hormone, 3, 3′, 5-triiodo-L-thyronine (T 3), mediates cell growth, development and differentiation by binding to its nuclear receptors (TRs). The role of TRs in cancer is still undefined. Notably, hyperthyroxinemia has been reported to influence the rate of colon cancer in an experimental model of carcinogenesis in rats. Previous microarray analysis revealed that cathepsin H (CTSH) is upregulated by T 3 in HepG2-TR cells. We verified that mRNA and protein expression of CTSH are induced by T 3 in HepG2-TR cells and in thyroidectomized rats following administration of T 3. The possible thyroid hormone-responsive elements of the CTSH promoter localized to the nucleotides-2038 to-1966 and-1565 to-1501 regions. An in vitro functional assay showed that CTSH can increase metastasis. J7 cells overexpressing CTSH were inoculated into severe combined immune-deficient mice and these J7-CTSH mice displayed a greater metastatic potential than did J7-control mice. The clinicopathologic significance of CTSH expression in hepatocellular carcinoma (HCC) was also investigated. The CTSH overexpressing in HCC was associated with the presence of microvascular invasion (P0.037). The microvascular invasion characteristic is closely related to our in vitro characterization of CTSH function. Our results show that T 3-mediated upregulation of CTSH led to matrix metallopeptidase or extracellular signal-regulated kinase activation and increased cell migration. This study demonstrated that CTSH overexpression in a subset hepatoma may be TR dependent and suggests that this overexpression has an important role in hepatoma progression.
原文英語
頁(從 - 到)2057-2069
頁數13
期刊Oncogene
30
發行號17
DOIs
出版狀態已發佈 - 四月 28 2011

ASJC Scopus subject areas

  • 分子生物學
  • 癌症研究
  • 遺傳學

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