(52), showed in MELN (cells derived from MCF-7 cells) spheroids that E2 (1 nM, from 4 to 23 days incubation) induced a proliferation proteins gradient from MCTS periphery (higher content of Ki67- and cyclinD1- positive cells) to the center (low content of Ki67- and cyclin D1-positive cells), which may help explaining why E2 stimulates cell cycle in cancer spheroids. The gene discussed is CCND1; the disease is cancer.