Department of Microbiology and Immunology, New York Medical College, Valhalla, New York 10595, USA.
Thyroid. 2010 Jan;20(1):33-41. doi: 10.1089/thy.2009.0296.
Over 200 million people worldwide are affected by thyroid proliferative diseases, including cancer, adenoma, and goiter, annually. The incidences of thyroid malignancies are three to four times higher in women, suggesting the possible involvement of estrogen. Based on this observed sex bias, we hypothesize that estrogen modulates the growth and metastatic propensity of thyroid cancer cells.
In this study, two thyroid cell lines (Nthy-ori 3-1 and BCPAP) were evaluated for the presence of estrogen receptor (ER) by Western blot analysis and estrogen responsiveness by using a cell proliferation assay. In addition, the effect of estradiol (E(2)) on modulation of metastatic phenotype was determined by using in vitro adhesion, migration, and invasion assays.
Thyroid cells expressed a functionally active ER-alpha and ER-beta as evidenced by 50-150% enhancement of proliferation in the presence of E(2). E(2) also enhanced adhesion, migration, and invasion of thyroid cells in an in vitro experimental model system that, based on our results, is modulated by beta-catenin.
Our data provide evidence that the higher incidence of thyroid cancer in women is potentially attributed to the presence of a functional ER that participates in cellular processes contributing to enhanced mitogenic, migratory, and invasive properties of thyroid cells. These findings will enable and foster the possible development of antiestrogenic therapy targeting invasion and migration, thus affecting metastatic propensity.
全球有超过 2 亿人受到甲状腺增生性疾病的影响，包括癌症、腺瘤和甲状腺肿，每年。女性甲状腺恶性肿瘤的发病率是男性的三到四倍，这表明雌激素可能参与其中。基于这种观察到的性别偏见，我们假设雌激素调节甲状腺癌细胞的生长和转移倾向。
在这项研究中，通过 Western blot 分析评估了两种甲状腺细胞系（Nthy-ori 3-1 和 BCPAP）中雌激素受体（ER）的存在，并通过细胞增殖测定评估了雌激素反应性。此外，通过体外粘附、迁移和侵袭测定确定了雌二醇（E2）对调节转移表型的影响。
甲状腺细胞表达功能性 ER-α和 ER-β，这一点可以通过 E2 的存在增强增殖 50-150%来证明。E2 还增强了甲状腺细胞在体外实验模型系统中的粘附、迁移和侵袭，根据我们的结果，该系统受β-连环蛋白调节。
我们的数据提供了证据表明，女性中甲状腺癌发病率较高可能归因于功能性 ER 的存在，该受体参与了促进甲状腺细胞有丝分裂、迁移和侵袭特性的细胞过程。这些发现将为针对侵袭和迁移的抗雌激素治疗的开发提供依据和支持，从而影响转移倾向。
