Although current evidence suggests primarily that mitogenic signaling regulates D-cyclins in a unidirectional pathway to activate E2F-dependent activation of cell cycle progression, consistent with our findings, Ginsberg et al. demonstrated a possible feedback loop whereupon E2F gene targets include effectors of the MAPK and Akt pathway in osteosarcoma cells [53,54]. Here, AKT1 is linked to osteosarcoma.