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; Kim, Sang-Hoon; Choi, Kwang-Soo; Kang, Chang-Won

Korean Journal of Veterinary Research 2006;46(2):97-105.

Sun-Mi Lee¹, Sang-Hoon Kim¹, Kwang-Soo Choi², Chang-Won Kang¹

¹Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University
²Department of Animal Resources Science, Woosuk University

MCF-7 cell에서 all-trans retinoic acid에 의한 insulin-like growth factor-I와 insulin-like growth factor binding protein-3 분비조절에 있어서 PKC-δ의 역할

이선미¹, 김상훈¹, 최광수², 강창원¹

¹전북대학교 수의과대학 생체안전성연구소
²우석대학교 동물자원학과

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.

Key Words: AtRA, IGF-I, MCF-7, IGFBP-3, PKC-${delta}$