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All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addtion, we investigated the involvement of PKC-d on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA( ? 10-7 M) decreased the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). 10-7 M AtRA activated PKC-d that is one among PKC-i, a, l and d in MCF-7 cell. Rotllerin, a PKC-d inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of IGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA- induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-d activity.