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The roles of PKC-δ on the regulation of insulin-like growth factor(IGF)-I and insulin-Like growth factor binding protein-3 secretion by all-trans retinoic acid in MCF-7 cell  

Lee, Sun-Mi (Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Kim, Sang-Hoon (Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Choi, Kwang-Soo (Department of Animal Resources Science, Woosuk University)
Kang, Chang-Won (Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Publication Information
Korean Journal of Veterinary Research / v.46, no.2, 2006 , pp. 97-105 More about this Journal
Abstract
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 addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 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-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-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-${\delta}$ activity.
Keywords
AtRA; IGF-I; MCF-7; IGFBP-3; PKC-${\delta}$;
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