Overexpression of Wild-type THRβ1 Suppresses the Growth and Invasiveness of Human Papillary Thyroid Cancer Cells

Abstract

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. Materials and Methods: Using an adenoviral delivery system, THRβ1 was expressed in human papillary thyroid cancer cell lines and corresponding biological and molecular changes were analyzed. Results: THRβ1-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. Conclusion: The alteration of THRβ1 functioning is an important change in human well-differentiated thyroid carcinomas, affecting tumor cell growth and contributing to the malignant potential of cancer cells.