Departamento de Ciências Básicas da Saúde (DCBS) e Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil.
Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil.
Mol Cell Endocrinol. 2021 Sep 15;535:111397. doi: 10.1016/j.mce.2021.111397. Epub 2021 Jul 14.
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.
甲状腺乳头状癌（PTC）近年来发病率不断上升，女性更为多发。实验研究表明，雌激素可能是女性发病率较高的一个重要危险因素。事实上，已有研究表明 17β-雌二醇（E2）可促进甲状腺滤泡细胞增殖和去分化。基因组雌激素反应通常通过经典的雌激素受体（α和β亚型）介导，在正常和异常人类甲状腺组织中均有描述。然而，在一些甲状腺癌细胞系中描述的 G 蛋白偶联雌激素受体 1（GPR30/GPER/GPER1）介导的作用，可能部分负责调节正常细胞的生长。在这项研究中，描述了非恶性和甲状腺乳头状癌（PTC）中的 GPER1 基因和蛋白表达，并分析了其与 PTC 患者临床特征的关系。在 PTC 的新鲜样本中以及 GEO 和 TCGA 数据库的计算分析中，与配对的非恶性甲状腺组织相比，PTC 中的 GPER1 表达较低。在 TCGA 数据库的 PTC 病例中，低水平的 GPER1 mRNA 表达与转移性淋巴结、女性性别和 BRAF 突变独立相关。此外，GPER1 mRNA 水平与甲状腺分化基因的 mRNA 水平呈正相关。这些结果支持了 GPER1 在 PTC 肿瘤发生中的作用的假说，并且可能是其治疗的潜在靶点。需要进一步的研究来确定这些受体在正常和患病甲状腺中的功能。
