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Figure 5: Proposed interaction between 1, 25-D3 and IGFBP-3 in MCF-7 and MCF-7/VDR cells. In parental cells stimulation by 1, 25-D3 of IGFBP-3 secretion attenuates IGF-1-induced activation of Akt, leading to apoptosis. In addition, 1, 25-D3 may initiate caspase-independent pathways contributing to cell death in parental cells. In resistant cells, failure of IGFBP-3 secretion is associated with activation of the IGF-I/Akt pathway, leading to cell survival.