Poorly differentiated, metastatic
thyroid cancer is difficult to treat. These
tumors often do not concentrate radioactive
iodine and may require
chemotherapy, which is suboptimal and toxic.
Nuclear hormone receptors peroxisome proliferator-activated receptor gamma (
PPARgamma) and
retinoid X receptor (RXR) are variably expressed in
thyroid carcinoma cell lines. Expression of these receptors may predict
thyroid cancer cell response to treatment with rexinoids and
thiazolidinediones. We studied three
thyroid carcinoma cell lines: BHP 5-16 (
PPARgamma-/RXRgamma+), BHP 2-7 (
PPARgamma+/-/RXRgamma-), and DRO-90 (RXRgamma+/
PPARgamma+). BHP 5-16 (RXRgamma+) cells treated with rexinoid had decreased proliferation to 69 +/- 6% growth compared with vehicle. BHP 2-7 (
PPARgamma+) cells treated with
thiazolidinedione had no decrease in cellular proliferation. DRO-90 (RXRgamma+ and
PPARgamma+) cells had 36 +/- 10%, 15 +/- 3%, and 13 +/- 4% growth when treated with rexinoid,
thiazolidinedione, or a combination, respectively. We next investigated the role of apoptosis in the
ligand-responsive BHP 5-16 and DRO-90 cells. BHP 5-16 cells underwent no significant apoptosis with rexinoid (1 micromol/L). DRO-90 cells, however, had 3.6 +/- 1.3% apoptotic cells with vehicle, 13 +/- 3.5% with rexinoid (1 micromol/L), 18 +/- 4% with
thiazolidinedione (1 micromol/L), and 28 +/- 6% with combination treatment (1 micromol/L), suggesting that apoptosis plays a major role in this anaplastic cell line and that the effects of the two
ligands are additive. We conclude that receptor expression is necessary for inhibition of
thyroid carcinoma growth with
ligand treatment but may not be sufficient for response. Additionally, expression of both RXRgamma and
PPARgamma may be necessary for maximal growth inhibition by
ligands and may be required for the increased apoptosis.