Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels

Delafontaine, Patrick; Song, Yao‐Hua; Li, Yangxin

doi:10.1161/01.atv.0000105902.89459.09

Cited by 487 publications

(405 citation statements)

References 180 publications

(176 reference statements)

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“…We found, for the first time, that variant genotype of rs5742612 were not associated with risk of GC. It is well-known that IGF-1 has significant roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis (Delafontaine et al, 2004). The majority of studies investigation correlation between circulating levels of IGF-1 and risk of cancers, but the association of IGF-1 single nucleotide polymorphism with cancer risk has been limited.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

Farahani

Azimzadeh²,

Rostami³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

Farahani

Azimzadeh²,

Rostami³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Ultimately, this inhibits the transcription of Egr-1 and its target genes, including bFGF and PDGF. Because IGFBP-3 has been shown to inhibit vascular endothelial cell survival 45,46 and induce tumor vasculature normalization, 47 it is believed to have antiangiogenic properties. In support of this notion, IGFBP-3-mediated antitumor activities have been found to involve angiogenesis suppression in various cancer types.…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1–mediated transcriptional events

Kim

Choi

Lee

et al. 2011

Blood

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Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGFindependent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non-small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3-treated non-small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3-induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. IntroductionAngiogenesis, the formation of new capillaries from existing blood vessels, is essential to carcinogenic processes, including solid tumor formation, growth, invasion, and metastasis. 1 Most tumors can stimulate angiogenesis by switching on the production of numerous cytokines and growth factors, including fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs), and platelet-derived growth factors (PDGFs). 2 Several antiangiogenic agents are in various phases of clinical trials for human cancer; however, most of these agents target the VEGF signaling pathway. 3 Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated.Insulin-like growth factor-binding protein-3 (IGFBP-3), a member of a family of 6 IGFBPs, has demonstrated antiproliferative, proapoptotic, antiangiogenic, and antimetastatic activity in a variety of cancer cells. [4][5][6][7][8] It may also have IGF-independent antitumor activities through cell-surface or intracellular protein interaction, its nuclear translocation, or its transcriptional regulation. 7,[9][10][11][12] However, the mechanisms that mediate IGFBP-3's IGF-independent antitumor activity have not been clearly defined.The 82-kDa phosphoprotein transcription factor early growth response protein 1 (Egr-1), an immediate early gene product, has been implicated in multiple cellular processes, including cell growth, apoptosis, wound healing, and angiogenesis. Mitogenic stimuli, including serum, PDGF, peptide growth factors, and B-Raf, and nonmitogenic stresses, including ␥-irradiation and hypoxia, activate Egr-1 expre...

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“…Although certain members of the IGFBP family may have both stimulatory and inhibitory activity, IGFBP-4 has been predominately associated with inhibitory activity by reducing IGF-1R signaling (19,20,35,36). IGF-1R signaling has been shown to regulate cellular behavior by modulating processes such as proliferation, survival, and differentiation (36,37). Therefore, we sough to examine whether the ability of IGFBP-4 to inhibit IGF-1-and FGF-2-induced angiogenesis was associated with alterations in blood vessel proliferation.…”

Section: Reduced Proliferation Detected Within Igf-1-and Fgf-2-inducementioning

confidence: 99%

Insulin-like Growth Factor Binding Protein-4 Differentially Inhibits Growth Factor-induced Angiogenesis

Contois

Nugent

Caron

et al. 2012

Journal of Biological Chemistry

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Background:We examined the impact of insulin-like growth factor binding protein-4 (IGFBP-4) on growth factor-induced angiogenesis in vivo. Results: IGFBP-4 inhibited IGF-1 and FGF-2, but not VEGF-induced angiogenesis, and this inhibition depended on p38 MAPK activity. Conclusion:The anti-angiogenic activity of IGFBP-4 depends in part on p38 MAPK. Significance: New insight is provided into how blood vessels respond to endogenous inhibitors during growth factor-stimulated angiogenesis.

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Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels

Cited by 487 publications

References 180 publications

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1–mediated transcriptional events

Insulin-like Growth Factor Binding Protein-4 Differentially Inhibits Growth Factor-induced Angiogenesis

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