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Published on: August 23, 2019
Expression of thyroid hormone receptor isoforms down-regulated by thyroid hormone in human medulloblastoma cells
Tsuyoshi Monden1, Yasuyo Nakajima, Tetsu Hashida
1Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Tochigi, Japan.
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.
Insights
Thyroid hormone (T3) affects thyroid hormone receptor (TR) expression in medulloblastoma cells. T3 down-regulates TR mRNA levels, indicating post-transcriptional regulation at the RNA stability level.
Area of Science:
- Neuro-oncology
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormone is crucial for central nervous system development, including the cerebellum.
- The impact of thyroid hormone on cerebellar malignant tumors is not well understood.
Purpose of the Study:
- To investigate thyroid hormone receptor (TR) isoform expression in human medulloblastoma cells.
- To determine the effects of thyroid hormone (T3) on TR expression in these cells.
Main Methods:
- Northern blot and RT-PCR were used to detect TR isoform mRNA expression in HTB-185 cells.
- Cells were treated with T3, actinomycin D, and cycloheximide to assess TR mRNA regulation.
Main Results:
- TRalpha2 mRNA was detected, while TRalpha1 and TRbeta1 were detected by RT-PCR, and TRbeta2 was not expressed.
- T3 treatment decreased TRalpha1, TRalpha2, and TRbeta1 mRNA levels.
- T3 influenced TR mRNA stability and required new protein synthesis for down-regulation.
Conclusions:
- Thyroid hormone down-regulates TR expression in medulloblastoma cells.
- TR expression is post-transcriptionally regulated by T3, primarily at the level of RNA stability.
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