Extract

ABSTRACT

We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2+/− mice are in a hypothyroid state. To clarify the mechanism, we studied the effects of small interfering RNA-mediated silencing of Runx2 on thyroid-specific gene expression in FRTL-5 cells. Lowering the levels of Runx2 had no effect on the amount of Na+/I symporter mRNA but markedly decreased the amount of thyroglobulin (Tg) mRNA. A Runx2 binding consensus sequence is present on the Tg gene promoter, and gel-shift assay revealed that Runx2 binds to this region. Reporter assay showed that deletion of the region or introduction of a mutation into the binding site significantly impairs promoter function. These results indicate that Runx2 deficiency in mice causes decreased Tg expression and a novel type of hypothyroidism.

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