Overexpression of wild-type THRbeta1 suppresses the growth and invasiveness of human papillary thyroid cancer cells.
BACKGROUND
Thyroid hormone receptors (THRs) are transcription factors which regulate cell growth and differentiation. The compromised function of THRs has been reported in several human malignancies, suggesting their implication in carcinogenesis.


METHODS
Using an adenoviral delivery system, THRbeta1 was expressed in human papillary thyroid cancer cell lines and corresponding biological and molecular changes were analyzed.


RESULTS
THRPbeta1-dependent transactivation activity is diminished in thyroid cancer cell lines. Its restoration suppresses the proliferation, causes G1 arrest, depresses DNA synthesis and decreases invasiveness of cancer cells paralleled by the attenuation of AKT and MAPK signaling, and reduction of cyclin D1 levels.


CONCLUSIONS
The alteration of THRbeta1 functioning is an important change in human well-differentiated thyroid carcinomas, affecting tumor cell growth and contributing to the malignant potential of cancer cells.
Sedliarou
Ilya
I
Departments of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Matsuse
Michiko
M
Saenko
Vladimir
V
Rogounovitch
Tatiana
T
Nakazawa
Yuka
Y
Mitsutake
Norisato
N
Namba
Hiroyuki
H
Nagayama
Yuji
Y
Yamashita
Shunichi
S
D000256:Adenoviridae / Q000235:genetics; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000096:biosynthesis* / Q000235:genetics; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015533:Transcriptional Activation; D014162:Transfection
D037042:Thyroid Hormone Receptors beta; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1