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http://dx.doi.org/10.7314/APJCP.2012.13.4.1183

Effect of Insulin-like Growth Factor-1 on Bone Morphogenetic Protein-2 Expression in Hepatic Carcinoma SMMC7721 Cells through the p38 MAPK Signaling Pathway  

Xu, Guan-Jun (Department of Oncology, the Second Affiliated Hospital of Nanchang University)
Cai, Sheng (Department of Oncology, the Second Affiliated Hospital of Nanchang University)
Wu, Jian-Bing (Department of Oncology, the Second Affiliated Hospital of Nanchang University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1183-1186 More about this Journal
Abstract
Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.
Keywords
Insulin-like growth factor-1; BMP-2; p38 MAPK; hepatic carcinoma;
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1 Chen FM, Chen R, Wang XJ, Sun HH, Wu ZF (2009). In vitro cellular responses to scaffolds containing two microencapulated growth factors. Biomaterials, 30, 5215-24.   DOI
2 Date T, Doiguchi Y, Nobuta M, Shindo H (2004). Bone morphogenetic protein-2 induces differentiation of multipotent C3H10T1/2 cells into osteoblasts, chondrocytes, and adipocytes in vivo and in vitro. Orthop Sci, 9, 503-8.
3 Furundzija V, Fritzsche J, Kaufmann J, et al (2010). IGF-1 increases macrophage motility via PKC/p38-dependent alphavbeta3-integrin inside-out signaling. Biochem Biophys Res Commun, 394, 786-91.   DOI
4 Graham TR, Odero-Marah VA, Chung LW, et al (2009). PI3K/ Akt-dependent transcriptional regulation and activation of BMP-2-Smad signaling by NF-kappa B in metastatic prostate cancer cells. Prostate, 69, 168-80.   DOI
5 Guicheux J, Lemonnier J, Ghayor C, et al (2003). Activation of p38 mitogen-activated protein kinase and c-Jun-NH2- terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. Bone Miner Res, 18, 2060-8.   DOI   ScienceOn
6 Gutierrez J, Parrizas M, Maestro MA, Navarro I, Plisetskaya EM (1995). Insulin and IGF-I binding and tyrosine kinase activity in fish heart. Endocrinol, 146, 35-44.   DOI
7 Jones JI, Clemmons DR (1995). Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev, 16, 3-34.
8 Martin MM, Buckenberger JA, Jiang J, et al (2007). TGF-${\beta}1$ stimulates human AT1 receptor expression in lung fibroblasts by cross talk between the Smad, P38MAPK, JNK, and PI3K signaling Pathways. Am J Physiol Lung Cell Mol Physiol, 293, L790-9.   DOI
9 Mukherjee A, Rotwein P (2009). Akt promotes BMP2-mediated osteoblast differentiation and bone development. Cell Sci, 122, 716-26.   DOI
10 Mukherjee A, Wilson EM, Rotwein P (2010). Selective signaling by Akt2 promotes bone morphogenetic protein 2-mediated osteoblast differentiation. Mol Cell Biol, 30, 1018-27.   DOI
11 Osyczka AM, Leboy PS (2005). Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology, 146, 3428-37.   DOI   ScienceOn
12 Nishimura R, Kato Y, Chen D, et al (1998). Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. Biol Chem, 273, 1872-9.   DOI
13 Noda T, Tokuda H, Yoshida M, et al (2005). Possible involvement of phosphatidylinositol 3-kinase/Akt pathway in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblasts. Horm Metab Res, 37, 270-4.   DOI
14 Noth U, Tuli R, Seghatoleslami R, et al (2003). Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts. Exp Cell Res, 291, 201-11.   DOI   ScienceOn
15 Raida M, Clement JH, Leek RD, et al (2005). Bone morphogenetie protein-2 (BMP-2) and induction of tumor angiogenesis. Cancer Res Clin Oncol, 131, 741-50.   DOI
16 Salehi Z, Mashayekhi F, Naji M, Pandamooz S (2009). Insulinlike growth factor-1 and insulin-like growth factor binding proteins in cerebrospinal fluid during the development of mouse embryos. J Clin Neurosci, 16, 950-3.   DOI
17 Santen RJ, Fan P, Zhang Z, et al (2009). Estrogen signals via an extra-nuclear pathway involving IGF-1R and EGFR in tamoxifen-sensitive and -resistant breast cancer cells. Steroids, 74, 586-94.   DOI
18 Steinert AF, Palmer GD, Pilapil C, et al (2009). Enhanced in vitro chondrogenesis of primary mesenchymal stem cells by combined gene transfer. Tissue Eng Part A, 15, 1127-39.   DOI
19 Wang X, Wenk E, Zhang X, et al (2009). Growth factor gradients via microsphere delivery in biopolymer scaffolds for osteochondral tissue engineering. Control Release, 134, 81-90.   DOI
20 Vinals F, Lopez-Rovira T, Rosa JL, Ventura F (2002). Inhibition of PI3K/p70 S6K and p38 MAPK cascades increases osteoblastic differentiation induced by BMP-2. FEBS Lett, 510, 99-104.   DOI
21 Wozney JM (1998). The bone morphogenetic protein family: multifunctional cellular regulators in the embryo and adult. Eur J Oral Sci, 106, 160-6.   DOI
22 Wu JB, Fu HQ, Huang LZ, Liu AW, Zhang JX. (2011). Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism. Cancer Gene Ther, 18, 20-5.   DOI
23 Xia Y, Babitt JL, Sidis Y, Chung RT, Lin HY (2008). Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood, 111, 5195-204.   DOI
24 Xu CP, Ji WM, van den Brink GR, Peppelenbosch MP (2006). Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver. World J Gastroenterol, 12, 7621-5.