The gene regulating activity of thyroid hormone nuclear receptors is modulated by cell-type specific factors

To understand whether the transcriptional activity of thyroid hormone nuclear receptors (TRs) is modulated by cell-type specific factors, full length TR subtype alpha 1 (TR alpha 1) and beta 1 (TR beta 1) 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 (T-3) and the thyroid hormone response elements (TREs) similarly to those cloned from other tissues. They exhibited T-3- and TRE-dependent transactivation activities, indicating these TRs were transcriptionally active. The lipogenic malic enzyme (ME), a T-3-target gene in Liver, was stimulated similar to 3- and 1.5-fold by T-3 in HA22T and SR-Hep-l, respectively. The T-3-stimulated ME gene expression was inhibited in HA22T, but stimulated in SH-Hep-l 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. (C) 1997 Academic Press.