Abstract:
:To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the beta-catenin-T-cell factor complex. This was confirmed biochemically, as beta-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a beta-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Miller LD,Park KS,Guo QM,Alkharouf NW,Malek RL,Lee NH,Liu ET,Cheng SYdoi
10.1128/mcb.21.19.6626-6639.2001subject
Has Abstractpub_date
2001-10-01 00:00:00pages
6626-39issue
19eissn
0270-7306issn
1098-5549journal_volume
21pub_type
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