A novel role for thyroid hormone receptor beta in cellular radiosensitivity.
Thyroid hormone receptors (THRs) widely govern cell growth, differentiation and metabolism acting in a ligand- and cofactor-dependent manner to modulate tissue-specific gene expression. Given a large variety of genes regulated by THRs and multiplicity of cellular processes potentially influenced by THRs, we addressed the role of THRB (thyroid hormone receptor beta) in cellular radiosensitivity. Wild-type and mutant THRB were overexpressed in several cell lines using an adenovirus-mediated gene delivery and their effects were examined after cell exposure to gamma-rays. Wild-type THRB decreased clonogenic survival of the cell lines with low levels of endogenous THRB, retarded their growth and synergized with radiation in decreasing proliferative potential and promoting cellular senescence. These changes were accompanied by the accumulation of p21 (CDKN1A, CIP1, WAF1) and p16 (CDKN2A, INK4a) inhibitors of cyclin-dependent kinases and by the decrease of Rb (retinoblastoma protein) phosphorylation. Mutant THRB produced a radioprotective effect, attenuated radiation-induced growth inhibition and cellular senescence. The results suggest that THRB may modulate cellular radiosensitivity and stress-induced senescence.
Matsuse
Michiko
M
Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Saenko
Vladimir
V
Sedliarou
Ilya
I
Rogounovitch
Tatiana
T
Nakazawa
Yuka
Y
Mitsutake
Norisato
N
Akulevich
Natallia
N
Namba
Hiroyuki
H
Yamashita
Shunichi
S
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002522:Chlorocebus aethiops; D005720:Gamma Rays; D018014:Gene Transfer Techniques; D006801:Humans; D009154:Mutation; D011836:Radiation Tolerance; D037042:Thyroid Hormone Receptors beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D037042:Thyroid Hormone Receptors beta