To understand whether the transcriptional activity of thyroid hormone nuclear receptors (TRs) is modulated by cell-type specific factors, full length TR subtype α1 (TRα1) and β1 (TRβ1) cDNAs were cloned from human hepatoma cell lines: HA22T, SK-Hep-1 and HepG2. The cloned receptor bound to the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) and the thyroid hormone response elements (TREs) similarly to those cloned from other tissues. They exhibited T3- and TRE-dependent transactivation activities, indicating these TRs were transcriptionally active. The lipogenic malic enzyme (ME), a T3-target gene in liver, was stimulated ~ 3- and 1.5-fold by T3 in HA22T and SK-Hep-1, respectively. The T3-stimulated ME gene expression was inhibited in HA22T, but stimulated in SK-Hep-1 cells by insulin. These results suggest that the gene regulating activity of TRs was modulated by cell-type specific factors. Furthermore, these cell-type specific factors could modulate the cross talk between TR- and insulin receptor-mediated pathways.
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 18 Sep 1997|