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A novel role for thyroid hormone receptor beta in cellular radiosensitivity
Michiko Matsuse1, Vladimir Saenko, Ilya Sedliarou
1Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Journal of Radiation Research
|October 30, 2007
Summary
Thyroid hormone receptor beta (THRB) influences cell response to radiation. Wild-type THRB increases radiosensitivity and senescence, while mutant THRB offers radioprotection, affecting cell survival and growth.
Area of Science:
- Molecular Endocrinology
- Radiation Biology
- Cellular Senescence
Background:
- Thyroid hormone receptors (THRs) regulate critical cellular functions including growth, differentiation, and metabolism.
- The specific role of thyroid hormone receptor beta (THRB) in cellular response to ionizing radiation remains largely unexplored.
Purpose of the Study:
- To investigate the impact of wild-type and mutant thyroid hormone receptor beta (THRB) on cellular radiosensitivity.
- To elucidate the mechanisms by which THRB modulates radiation-induced cellular responses, including growth inhibition and senescence.
Main Methods:
- Adenovirus-mediated gene delivery was used to overexpress wild-type and mutant THRB in various cell lines.
- Cells were exposed to gamma radiation, and effects on clonogenic survival, growth, senescence, and cell cycle regulators were analyzed.
Main Results:
- Overexpression of wild-type THRB decreased clonogenic survival and retarded cell growth in cell lines with low endogenous THRB levels.
- Wild-type THRB synergized with gamma radiation to reduce proliferative potential and promote cellular senescence, associated with p21 and p16 accumulation and decreased Rb phosphorylation.
- Mutant THRB exhibited radioprotective effects, attenuating radiation-induced growth inhibition and senescence.
Conclusions:
- Thyroid hormone receptor beta (THRB) plays a significant role in modulating cellular radiosensitivity.
- THRB influences stress-induced senescence and cell cycle regulation in response to ionizing radiation.
- The specific THRB isoform (wild-type vs. mutant) determines its effect on radiosensitivity, suggesting therapeutic potential.
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