Using mass spectrometry-based proteomic approach, we found that in ER+ BC mammospheres, exposure to lysine and E2 upregulated the splicing factor U2AF 35 kDa subunit (U2AF1) and ribophorin-2 (RPN2) proteins, which both were related to poor prognosis in BC patients. The gene discussed is U2AF1; the disease is breast cancer.