Troglitazone, the Peroxisome Proliferator-Activated Receptor-γ Agonist, Induces Antiproliferation and Redifferentiation in Human Thyroid Cancer Cell Lines

Abstract

Troglitazone is a potent agonist for the peroxisome proliferator-activated receptor-γ (PPARγ) that is a ligandactivated transcription factor regulating cell differentiation and growth. PPARγ may play a role in thyroid carcinogenesis since PAX8-PPARγ1 chromosomal translocations are commonly found in follicular thyroid cancers. We investigated the antiproliferative and redifferentiation effects of troglitazone in 6 human thyroid cancer cell lines: TPC-1 (papillary), FTC-133, FTC-236, FTC-238 (follicular), XTC-1 (Hürthle cell), and ARO82-1 (anaplastic) cell lines. PPARγ was expressed variably in these cell lines. FTC-236 and FTC-238 had a rearranged chromosome at 3p25, possibly implicating the involvement of the PPARγ encoding gene whereas the other cell lines did not. Troglitazone significantly inhibited cell growth by cell cycle arrest and apoptotic cell death. PPARγ overexpression did not appear to be a prerequisite for a response to treatment with troglitazone. Troglitazone also downregulated surface expression of CD97, a novel dedifferentiation marker, in FTC-133 cells and upregulated sodium iodide symporter (NIS) mRNA in TPC-1 and FTC-133 cells. Our investigations document that human thyroid cancer cell lines commonly express PPARγ, but chromosomal translocations involving PPARγ are uncommon. Troglitazone, a PPARγ agonist, induced antiproliferation and redifferentiation in thyroid cancer cell lines. PPARγ agonists may therefore be effective therapeutic agents for the treatment of patients with thyroid cancer that fails to respond to traditional treatments.