Positive regulation of spondin 2 by thyroid hormone is associated with cell migration and invasion

Chen Hsin Liao, Shih Chi Yeh, Ya-Hui Huang, Ruey Nan Chen, Ming Ming Tsai, Wei Jan Chen, Hsiang-Cheng Chi, Pei Ju Tai, Chia Jung Liao, Sheng Ming Wu, Wan Li Cheng, Li Mei Pai, Kwang Huei Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

48 Scopus citations

Abstract

The thyroid hormone 3,3′,5-triiodo-L-thyronine (T3) regulates growth, development, and differentiation processes in animals. These activities are mediated by the nuclear thyroid hormone receptors (TRs). Microarray analyses were performed previously to study the mechanism of regulation triggered by T3 treatment in hepatoma cell lines. The results showed that spondin 2 was regulated positively by T3. However, the underlying mechanism and the physiological role of T3 in the regulation of spondin 2 are not clear. To verify the microarray results, spondin 2 was further investigated using semi-quantitative reverse transcription-PCR and western blotting. After 48 h of T3 treatment in the HepG2-TRα1#1 cell line, spondin 2 mRNA and protein levels increased by 3.9-to 5.7-fold. Similar results were observed in thyroidectomized rats. To localize the regulatory region in spondin 2, we performed serial deletions of the promoter and chromatin immunoprecipitation assays. The T3 response element on the spondin 2 promoter was localized in the -1104/-1034 or -984/-925 regions. To explore the effect of spondin 2 on cellular function, spondin 2 knockdown cell lines were established from Huh7 cells. Knockdown cells had higher migration ability and invasiveness compared with control cells. Conversely, spondin 2 overexpression in J7 cells led to lower migration ability and invasiveness compared with control cells. Furthermore, this study demonstrated that spondin 2 overexpression in some types of hepatocellular carcinomas is TR dependent. Together, these experimental findings suggest that spondin 2, which is regulated by T3, has an important role in cell invasion, cell migration, and tumor progression.

Original languageEnglish
Pages (from-to)99-111
Number of pages13
JournalEndocrine-Related Cancer
Volume17
Issue number1
DOIs
StatePublished - 03 2010

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