Papillary thyroid cancer (PTC), whose incidence has been increasing in the last years, occurs more frequently in women. Experimental studies suggested that estrogen could be an important risk factor for the higher female incidence. In fact, it has been demonstrated that 17β-estradiol (E2) could increase proliferation and dedifferentiation in thyroid follicular cells. Genomic estrogen responses are typically mediated through classical estrogen receptors, the α and β isoforms, which have been described in normal and abnormal human thyroid tissue. Nevertheless, effects mediated through G protein estrogen receptor 1 (GPR30/GPER/GPER1), described in some thyroid cancer cell lines, could be partially responsible for the regulation of growth in normal cells. In this study, GPER1 gene and protein expression are described in non-malignant and in papillary thyroid cancer (PTC), as well as its association with clinical features of patients with PTC. The GPER1 expression was lower in PTC as compared to paired non-malignant thyroid tissues in fresh samples of PTC and in silico analysis of GEO and TCGA databases. In PTC cases of TCGA database, low GPER1 mRNA expression was independently associated with metastatic lymph nodes, female gender, and BRAF mutation. Besides, GPER1 mRNA levels were positively correlated with mRNA levels of thyroid differentiation genes. These results support the hypothesis that GPER1 have a role in PTC tumorigenesis and might be a potential target for its therapy. Further studies are needed to determine the functionality of these receptors in normal and diseased thyroid.
Keywords: 17β-estradiol; BRAF mutation; GPR30/GPER1/GPER; Metastatic lymph nodes; Papillary thyroid cancer; Tumor microenvironment.
Copyright © 2021 Elsevier B.V. All rights reserved.