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 alpha1 (TRalpha1) and beta1 (TRbeta1) 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 approximately 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.
Lin
K
K
Graduate Institute of Clinical Medicine, Chang-Gung College of Medicine and Technology, Taoyuan, Taiwan.
Chen
S l
Sl
Zhu
X G
XG
Shieh
H
H
McPhie
P
P
Cheng
S
S
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones