TGF-β-induced expression of IGFBP-3 regulates IGF1R signaling in human osteosarcoma cells

被引：44

作者：

Schedlich, Lynette J. ^{[1
]}

Yenson, Vanessa M. ^{[1
]}

Baxter, Robert C. ^{[1
]}

机构：

[1] Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, Sydney, NSW 2065, Australia

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2013年 / 377卷 / 1-2期

基金：

英国医学研究理事会;

关键词：

Osteosarcoma; Transforming growth factor-beta; Insulin-like growth factor; Insulin-like growth factor binding protein-3; Signaling; FACTOR-BINDING PROTEIN-3; BREAST-CANCER CELLS; GROWTH-FACTOR-I; RECEPTOR KINASE INHIBITOR; TRANSFORMING GROWTH-FACTOR-BETA-1; ANTITUMOR-ACTIVITY; TUMOR SUPPRESSION; SMAD; PATHWAYS; TRANSDUCTION;

D O I：

10.1016/j.mce.2013.06.033

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Signaling pathways initiated by transforming growth factor-beta (TGF-beta) and insulin-like growth factors (IGFs) are important in osteosarcoma cell growth. We have investigated a role for endogenous IGF binding protein-3 (IGFBP-3) in mediating cross-talk between TGF-beta receptor and type I IGF receptor (IGF1R) signaling pathways in MG-63 osteosarcoma cells. TGF-beta 1 indirectly activated the Ras/Raf/MAPK pathway and induced the expression of IGFBP-3, an important regulator of IGF1R activity. IGFBP-3 attenuated TGF-beta 1 activation of ERK1/2 and Akt in MG-63 cells, and inhibited TGF-beta 1-induced cell cycle progression and proliferation. This effect of IGFBP-3 was blocked by inhibiting IGF1R signaling. TGF-beta 1 phosphorylated Smad2 on the non-receptor substrate sites (Ser245/250/255). Blocking the TGF-beta 1-induced expression of IGFBP-3 enhanced pSmad2(Ser245/250/255) and increased its nuclear accumulation. These results suggest an important role for TGF-beta 1 in osteosarcoma cell growth, with the induction of IGFBP-3 by TGF-beta 1 serving in a negative-feedback loop to control cell growth by preventing activation of the IGF1R. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：56 / 64

页数：9

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