Differential Effects Of Estrogen Receptor Alpha And Beta On Endogenous Ligands Of Peroxisome Proliferator-Activated Receptor Gamma In Papillary Thyroid Cancer

PurposeThe inhibition of estrogen receptor alpha (ER alpha) or the activation of ER beta can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ER alpha and ER beta on the production of endogenous peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands in PTC.

Methods2 PTC cell lines, 32 pairs of PTC tissues and matched normal thyroid tissues were used in this study. The levels of endogenous PPAR gamma ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Delta 12,14-prostaglandin J2 (PGJ2) were measured by ELISA.

ResultsThe levels of PGJ2 and 15(S)-HETE were significantly reduced in PTC, but 13(S)-HODE was not changed. Activation of ER alpha or inhibition of ER beta significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ER alpha or activation of ER beta markedly upregulated the production of these three ligands. Application of endogenous PPAR gamma ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy.

ConclusionThe levels of endogenous PPAR gamma ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ER alpha or activation of ER beta can inhibit PTC by stimulating the production of endogenous PPAR gamma ligands to induce apoptosis in cancer cells.