Differential Effects of Estrogen Receptor Alpha and Beta on Endogenous Ligands of Peroxisome Proliferator-Activated Receptor Gamma in Papillary Thyroid Cancer

Abstract

PurposeThe inhibition of estrogen receptor alpha (ERα) or the activation of ERβ can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ERα and ERβ on the production of endogenous peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Δ12,14-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 ERα or inhibition of ERβ significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ERα or activation of ERβ markedly upregulated the production of these three ligands. Application of endogenous PPARγ ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy.ConclusionThe levels of endogenous PPARγ ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ERα or activation of ERβ can inhibit PTC by stimulating the production of endogenous PPARγ ligands to induce apoptosis in cancer cells.

Application of dual‐source computed tomography in the diagnosis of thyroid cancer and evaluation of biological behaviors

“…Prior research has reported that suppression of ERα or activation of ERβ can inhibit TC development by inducing the apoptosis of TC cells 24 . The Ki‐67 proliferation index reflects the malignant behavior of TC 25 .…”

“…ERα and ERβ are involved in the progression of TC, playing opposite roles in the growth of TC cells, 24 and upregulation of ERα/ERβ protein ratio facilitates the papillary TC development 39 . Low ERβ expression is associated with poor survival in follicular TC, 40 and its expression is lower in papillary TC tumor tissues than in adjacent normal thyroid tissues 41 .…”

“…Prior research has reported that suppression of ERα or activation of ERβ can inhibit TC development by inducing the apoptosis of TC cells. 24 The Ki-67 proliferation index reflects the malignant behavior of TC. 25 Therefore, the positive expression rates of ERα, ERβ, and Ki67 in pathological sections of TC patients and benign patients were determined by immunohistochemistry, which evinced that TC patients exhibited higher positive expression rates of ERα and Ki67…”

Bioinformatics analysis reveals the potential target of rosiglitazone as an antiangiogenic agent for breast cancer therapy

“…Crosstalk between PPARG and ER suppresses the proliferation and migration of thyroid cancer cells [ 106 ]. In contrast, stimulation of PPARγ signaling leads to ER inhibition and induces apoptosis in papillary thyroid cancer cells [ 107 ]. Overexpression of HER2 induces upregulation of PPARG transcription and translation in ER+ MCF-7 cells [ 108 ].…”

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer

“…ERa induced prosurvival autophagy through generating the reactive oxygen species and activating ERK1/2 in thyroid cancer (14). In addition, we also reported that the differential role of ERa and ERb in thyroid cancer mediated the production of endogenous PPAR-g ligand (15). Upregulated ERa/ ERb ratio by PES1 will promote the occurrence and development of papillary thyroid cancer (PTC) (16).…”