tailieunhanh - Báo cáo khoa học: Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor-dependent manner

Thyroid hormone has various effects on cell proliferation, growth and apoptosis. To gain more insight into the molecular dynamics caused by thyroid hormone, gene expression in HeLaTRcells that constitutively over-expressed the thyroid hormone receptor (TR) was analyzed. Gene expression profiling of the HeLaTRcells with an oligonucleotide microarray yielded 229 genes whose expression was significantly altered by T3. | Eur. J. Biochem. 270 3064-3073 2003 FEBS 2003 doi Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor-dependent manner Toshiko Yamada-Okabe1 Yasuo Satoh2 and Hisafumi Yamada-Okabe1 3 1 Department of Hygiene department of Surgery School of Medicine Yokohama City University Fukuura Kanazawa Yokohama 3Pharmaceutical Research Department 4 Kamakura Research Laboratories Chugai Pharmaceutical Co. Ltd Kajiwara Kamakura Kanagawa Japan Thyroid hormone has various effects on cell proliferation growth and apoptosis. To gain more insight into the molecular dynamics caused by thyroid hormone gene expression in HeLaTR cells that cssistitulively overexpressed the thyroid hormone receptor TR was analyzed. Gene expression profiling of the HeLaTR cells with an oligonucleotide microarray yielded 229 genes whose expression was significantly altered by T3. Among these genes the expression of 4-1BB which is known to initiate a signal cascade activating NF-kB was significantly up-regulated by T3. Although treatment of the HeLaTRcells with T3 did not induce expression of NF-kB reporter luciferase even in the presence of the 4-1BB-Ligand it increased the caspase activities. An increase in the caspase activities was also observed in the HeLaTR eells rn nseected with 4-1BB cDNA and the 4-1BB-Ligand further increased the caspase activities of the HeLaTRcells overexpressing the 4-1BB. Furthermore up-regulation of 4-1BB and an increase in caspase activities also occurred in the rat FRTL cells that expressed only authentic TR. These results demonstrate that the expression of 4-1BB serves as the mediator of signals from T3 to activate caspases. Keywords thyroid hormone thyroid hormone receptor 4-1BB gene expression apoptosis caspase. Thyroid hormone plays an important role in metabolism growth and development in a wide variety of organisms. Thyroid hormone is involved in the regulation of the lifecycle of .