Activation of estrogen receptor induces differential proteomic responses mainly involving migration, invasion, and tumor development pathways in human testicular embryonal carcinoma NT2/D1 cells

The aims of the present study were to investigate the global changes on proteome of human testicular embryonal carcinoma NT2/D1 cells treated with 17 beta-estradiol (E2), and the effects of this hormone on migration, invasion, and colony formation of these cells. A quantitative proteomic analysis identified the presence of 1230 proteins in both E2-treated and control cells. The analysis revealed 75 differentially abundant proteins (DAPs), out of which 43 proteins displayed a higher abundance and, 30 proteins showed a lower abundance in E2-treated NT2/D1 cancer cells. Functional analysis using IPA highlighted some activation processes such as migration, invasion, metastasis, and tumor growth. Interestingly, the treatment with E2 and ER beta-selective agonist DPN increased the migration of NT2/D1 cells. On the other hand, ER alpha-selective agonist PPT did not modify cell migration, indicating that ER beta is the upstream receptor involved in this process. The activation of ER beta increased the invasion and anchorage-independent growth of NT2/D1 cells more intensely than ER alpha. ER alpha and ER beta may play overlapping roles on invasion and colony formation of these cells. Further studies are required to clarify the mechanism underlying these effects. The molecular mechanisms revealed by proteomic and functional studies might also guide the development of potential targets for a better understanding of the biology of these cells and novel treatments for non-seminoma in the future.