title: Expression of thyroid hormone receptor isoforms down-regulated by thyroid hormone in human medulloblastoma cells.
abstract: The role of thyroid hormone (T3) in the regulation of growth and development of the central nervous system including the cerebellum has been well established. However, the effects of thyroid hormone on malignant tumors derived from the cerebellum remain poorly understood. Our analysis mainly focused on expression levels of TR isoforms and the effects of thyroid hormone in human medulloblastoma HTB-185 cells. Northern blot analysis revealed TRalpha2 mRNA but not TRalpha1, beta1 or beta2 mRNA in the cell. The TRalpha1 and TRbeta1 mRNAs were detected only by RT-PCR method and TRbeta2 was not expressed. Incubation of T3 for 24 h decreased TRalpha1, TRalpha2 and TRbeta1 mRNA. Addition of actinomycin D caused an acute increase in the basal TR mRNA levels and the rate of decrease of all kinds of TR isoform mRNA was accelerated in the T3-treated groups compared to controls, indicating that the stability of TR mRNA was affected by T3. Incubation with cycloheximide also blocked a decrease in TR mRNA levels in the T3-treated HTB-185 cells suggesting that down-regulation of TR mRNA required the synthesis of new protein. Our data provide novel evidence for the expression of TRs down-regulated by T3 in HTB-185 cells, suggesting that TR expression is post-transcriptionally regulated by T3 at the level of RNA stability.
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Tochigi, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Monden
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hashida
authors.forename: Sumiyasu
authors.initials: S
authors.lastname: Ishii
authors.forename: Takuya
authors.initials: T
authors.lastname: Tomaru
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibusawa
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Teturou
authors.initials: T
authors.lastname: Satoh
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Kikuo
authors.initials: K
authors.lastname: Kasai
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine