ABSTRACT
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 17ß-estradiol (E2) could increase proliferation and dedifferentiation in thyroid follicular cells. Genomic estrogen responses are typically mediated through classical estrogen receptors, the α and ß 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.
Subject(s)
Computational Biology/methods , Down-Regulation , Receptors, Estrogen/genetics , Receptors, G-Protein-Coupled/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics , Case-Control Studies , Databases, Genetic , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Male , Mutation , Proto-Oncogene Proteins B-raf/genetics , Sex CharacteristicsABSTRACT
BACKGROUND: Thyroid cancer incidence has been increasing, acquiring a greater importance in health, especially of women, who are more frequently affected. As 17-ß-estradiol (E2) has been shown to have a proliferative effect on benign and malignant thyroid cells, G protein-coupled estrogen receptor (GPER1) could have a role on the pathogenesis of thyroid cancer. OBJECTIVE: To evaluate data on GPER1 in the thyroid. DATA SOURCES: PubMed, Scielo and Cochrane Library databases were searched, using the keywords GPER1 or GPR30 or GPER and thyroid, since the inception until Jun, 2019. Other sources were used, as cross-referencing. STUDY SELECTION: All studies which evaluated GPER1 GPER1 or GPR30 or GPER in the thyroid. DATA EXTRACTION: From 23 articles identified, eight studies were included: one in commercial samples of human thyroid, four in human thyroid cancer cell lines, and three in human samples of benign and/or malignant thyroid diseases. DATA SYNTHESIS: GPER1 gene and protein expression were described, respectively, in six and five studies, and the results varied according to the study. In three studies, increased proliferation of four thyroid cancer cell lines were induced by E2, with evidences suggesting that GPER1 at least partially mediated growth in these cells. GPER1 was identified in the cell membrane, in three studies, and in the cytoplasm in two studies. CONCLUSIONS: The paucity of studies about GPER1 in the thyroid, as well as methodological differences between them, precludes firm conclusions about GPER1 role in the thyroid, although there are some evidences of GPER1-induced proliferation of thyroid cancer cells.
