Oestrogen mediates the growth of human thyroid carcinoma cells via an oestrogen receptor – ERK pathway


George G. Chen, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. Tel.: +852 26323934; Fax: +852 26450605; E-mail: gchen@cuhk.edu.hk


Abstract. Objectives: Although thyroid cancer occurs much more frequently in females, the role of sex hormones in thyroid carcinogenesis is unknown. In this study, it has been investigated how 17β-oestradiol (E2) influenced proliferation and growth of thyroid cancer cells. Materials and Methods: Cell proliferation and its related molecules were examined in thyroid papillary carcinoma cells (KAT5), follicular thyroid carcinoma cells (FRO) and anaplastic carcinoma cells (ARO). Levels of oestrogen receptor (ER) α and β were regulated by their agonists (PPT and DPN), antagonists and siRNA. Results: E2 promoted cell proliferation. Such an effect was positively related to ERα but negatively to ERβ; PPT enhanced cell proliferation while DPN inhibited it. PPT increased Bcl-2 expression while DPN decreased it. DPN also elevated Bax expression. PPT elevated the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), suggesting a positive role of ERK1/2 in E2-induced cell proliferation. Knockdown of ERα significantly attenuated E2-mediated Bcl-2 and pERK1/2 expression. In contrast, knockdown of ERβ markedly enhanced them. Conclusions: Oestrogen stimulates proliferation of thyroid cancer cells, associated with increase in Bcl-2 and decrease in Bax levels in an ERK1/2-related pathway. Imbalance between ERα and ERβ may contribute to thyroid carcinogenesis.