Estrogen Receptor Alpha Stimulates Reactive Oxygen Species to Induce Autophagy in Thyroid Papillary Cancer
George G Chen*, Shucai Yang, Jing Du, Zhongqin Gong, Lingbin Xue, Alexander C Vlantis, Jason Chan, C Andrew van Hasselt, Michael CF Tong
The Chinese University of Hong Kong, China
Citation: Chen GG, Yang S, Du J, Gong Z, Xue L et al (2021) Estrogen Receptor Alpha Stimulates Reactive Oxygen Species to Induce Autophagy in Thyroid Papillary Cancer. SciTech Biomed-Cancer Sciences 2021.
Received: December 02, 2020 Accepted: December 05, 2020 Published: December 05, 2020
Papillary Thyroid Cancer (PTC) accounts for more than 80% of thyroid cancers and it is dominant in female (femail:male = 3-4: 1), suggesting a role of sex hormones in its development. Increasing data have shown that Estrogen Receptor alpha (ERa) has a positive role in the growth/progression of PTC. Antioxidants are a buffering system to control the activity/level of reactive oxygen species (ROS), the role of which is debatable in PTC. The relationship between ERa and ROS remains elusive in PTC. In this study, we confirmed that the expression of ERa was increased in PTC tissue samples, compared with non-tumor thyroid tissues and that estrogen (E2) treatment could significantly stimulate the expression of ERa. We demonstrated that E2-mediated ERa elevation accompanied the upregulation of intracellular ROS measured by the oxidation-sensitive probe DCFH-DA. The increased ROS caused a significant elevation of the autophagy and enhanced the proliferation and survival of cancer cells. Moreover, we found that the level of antioxidants including manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), and glutathione peroxidase (Gpx) were increased in PTC tissue samples. In cell cultures, PTC cells treated with hydrogen peroxide (H2O2), a well-known source of ROS, markedly upregulated the levels of antioxidants. Since antioxidants functions to control the levels of ROS, thus, our findings suggest that the upregulation of antioxidants is likely a defensive deployment against the surge of ROS. Conclusion and Significance: PTC is associated with ERa upregulation as well as the increase of ROS. The upregulation of ERa can trigger the production of ROS, which is balanced by antioxidants to maintain the survival, promote the autophagy and enhance the growth of PTC. (This study was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region: 14109716).
Keywords: Papillary thyroid cancer, Reactive oxygen species, Estrogen receptor alpha, Autophagy