scholarly journals Radioresistant laryngeal cancers upregulate type 1 IGF receptor and exhibit increased cellular dependence on IGF and EGF signalling

2019 ◽  
Vol 44 (6) ◽  
pp. 1026-1036 ◽  
Author(s):  
Ali Qureishi ◽  
Guillaume Rieunier ◽  
Ketan A. Shah ◽  
Tamara Aleksic ◽  
Stuart C. Winter ◽  
...  
Keyword(s):  
Igf Receptor

scholarly journals The C Region of Human Insulin-like Growth Factor (IGF) I Is Required for High Affinity Binding to the Type 1 IGF Receptor

1989 ◽  
Vol 264 (19) ◽  
pp. 11004-11008 ◽  
Author(s):  
M L Bayne ◽  
J Applebaum ◽  
D Underwood ◽  
G G Chicchi ◽  
B G Green ◽  
...  
Keyword(s):  
Growth Factor ◽  
Human Insulin ◽  
Affinity Binding ◽  
Insulin Like Growth Factor ◽  
High Affinity Binding ◽  
High Affinity ◽  
Igf I ◽  
Igf Receptor

scholarly journals The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney disease

2011 ◽  
Vol 21 (5) ◽  
pp. 285-291 ◽  
Author(s):  
Ariel Troib ◽  
Daniel Landau ◽  
Jack F. Youngren ◽  
Leonid Kachko ◽  
Ralph Rabkin ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Receptor Inhibition ◽  
Igf Receptor

scholarly journals Des(1–3)IGF-1 Treatment Normalizes Type 1 IGF Receptor and Phospho-Akt (Thr 308) Immunoreactivity in Predegenerative Retina of Diabetic Rats

2003 ◽  
Vol 4 (1) ◽  
pp. 45-57 ◽  
Author(s):  
A. Kummer ◽  
B. E. Pulford ◽  
D. N. Ishii ◽  
G. M. Seigel
Keyword(s):  
Growth Factor ◽  
Ganglion Cell Layer ◽  
Systemic Treatment ◽  
Diabetic Rats ◽  
Vascular Endothelial ◽  
Diabetic Retina ◽  
Igf Receptor ◽  
Endothelial Growth Factor ◽  
Biochemical Abnormalities

Little is known about interventions that may prevent predegenerative changes in the diabetic retina. This study tested the hypothesis that immediate, systemic treatment with an insulin-like growth factor (IGF)-1 analog can prevent abnormal accumulations of type 1 IGF receptor, and phospho-Akt (Thr 308) immunoreactivity in predegenerative retinas of streptozotocin (STZ) diabetic rats. Type 1 IGF receptor immunoreactivity increased approximately 3-fold in both inner nuclear layer (INL) and ganglion cell layer (GCL) in retinas from STZ rats versus nondiabetic controls. Phospho-Akt (Thr 308) immunoreactivity increased 5-fold in GCL and 8-fold in INL of STZ rat retinas. In all cases, immunoreactive cells were significantly reduced in STZ des(1–3)IGF-1–treated versus STZ rats. Preliminary results suggested that vascular endothelial growth factor (VEGF) levels may also be reduced. Hyperglycemia/ failure of weight gain in diabetic rats continued despite systemic des(1–3)IGF-1. These data show that an IGF-1 analog can prevent early retinal biochemical abnormalities implicated in the progression of diabetic retinopathy, despite ongoing hyperglycemia.

scholarly journals Zinc partitions IGFs from soluble IGF binding proteins (IGFBP)-5, but not soluble IGFBP-4, to myoblast IGF type 1 receptors

2004 ◽  
Vol 180 (2) ◽  
pp. 227-246 ◽  
Author(s):  
RH McCusker ◽  
J Novakofski
Keyword(s):  
Cell Surface ◽  
Binding Sites ◽  
Affinity Binding ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Igf Receptor ◽  
Igf Binding Protein

Zinc (Zn(2+)), a multifunctional micronutrient, was recently shown to lower the affinity of cell-associated insulin-like growth factor (IGF) binding protein (IGFBP)-3 and IGFBP-5 for both IGF-I and IGF-II, but to increase the affinity of the cell surface type 1 IGF receptor (IGF-1R) for the same two ligands. However, there is a need for data concerning the effects of Zn(2+) on soluble IGFBPs and the type 2 IGF receptor (IGF-2R). In the current work, we demonstrate that Zn(2+) affects the affinity of IGFBP-5 secreted by myoblasts but not IGFBP-4. Zn(2+), at physiological levels, depressed binding of both IGF-I and IGF-II to IGFBP-5, affecting (125)I-IGF-I more than (125)I-IGF-II. Both (125)I-IGF-I and (125)I-IGF-II bound to high and low affinity sites on IGFBP-5. Zn(2+) converted the high affinity binding sites of IGFBP-5 into low affinity binding sites. An IGF-I analog, (125)I-R(3)-IGF-I, did not bind to the soluble murine IGFBP-5. Zn(2+) also decreased the affinity of the IGF-2R on L6 myoblasts. In contrast, Zn(2+) increased IGF-I, IGF-II and R(3)-IGF-I binding to the IGF-1R by increasing ligand binding affinity on both P(2)A(2a)-LISN and L6 myoblasts. Soluble IGFBP-5 and IGFBP-4 depressed the binding of (125)I-IGF-I and (125)I-IGF-II to the IGF-1R, but did not affect binding of (125)I-R(3)-IGF-I. By depressing the association of the IGFs with soluble IGFBP-5, Zn(2+) partitioned (125)I-IGF-I and (125)I-IGF-II from soluble IGFBP-5 onto cell surface IGF-1Rs. This effect is not seen when soluble L6-derived IGFBP-4 is present in extracellular fluids. We introduce a novel mechanism by which the trace micronutrient Zn(2+) may alter IGF distribution, i.e. Zn(2+) acts to increase IGF-1R binding at the expense of IGF binding to soluble IGFBP-5 and the IGF-2R.

Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells

1996 ◽  
Vol 134 (4) ◽  
pp. 474-480 ◽  
Author(s):  
Sylvie Babajko ◽  
Michel Binoux
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Protein Expression ◽  
Binding Protein ◽  
Neuroblastoma Cells ◽  
Insulin Like Growth Factor ◽  
Igf Binding ◽  
Igf Receptor ◽  
Igf Binding Protein

Babajko S, Binoux M. Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells. Eur J Endocrinol 1996;134:474–80. ISSN 0804–4643 Growth in neuroblastoma cells is regulated by insulin-like growth factors (IGFs) whose action is modulated by IGF binding proteins (IGFBPs). In this study, SK-N-SH neuroblastoma cells were shown to produce IGF-II, IGFBP-2, IGFBP-4 and small quantities of IGFBP-6. We have studied the effects of a natural morphogen, retinoic acid (RA), on growth and IGFBP expression in these cells. In all experiments, cells were cultured in serum-free medium and treated with 1 μmol/l RA for 12 h. Cell number increased by almost 50% during the first 24 h after the beginning of treatment. This stimulation was inhibited by 80% or more in the presence of the anti-type 1 IGF receptor antibody α-IR3 and anti-IGF-II antibody. The IGF-II concentrations in the culture media, measured after acidic gel filtration, increased about 1.5-fold and Northern blotting showed a concomitant increase in IGF-II mRNA levels. The mitogenic effect of RA therefore reflects its stimulation of IGF-II production. The availability of IGF-II to the cells may also be enhanced because of the proteolysis of IGFBP-2 to which it is bound. After this initial phase, proliferation ceased despite continued IGF-II production between 24 and 72 h. Both IGFBP-2 and IGFBP-4 production decreased, whereas that of IGFBP-6 increased. These changes appeared both in the protein quantities and in their mRNAs. Insulin-like growth factor binding protein 6 has a strong affinity for IGF-II, 5–10 times that of IGFBP-2 and at least 10 times that of the type 1 IGF receptor, and the arrested proliferation may result, at least in part, from sequestration by IGFBP-6 of the IGF-II secreted. Sylvie Babajko, INSERM U142, Hôpital Saint Antoine, 184 rue du Faubourg, St Antoine, 75571 Paris Cedex 12, France

Insulin-like growth factor-II and transforming growth factor-α in developing human fetal pancreatic islets

1993 ◽  
Vol 138 (1) ◽  
pp. 127-NP ◽  
Author(s):  
P. J. Miettinen ◽  
T. Otonkoski ◽  
R. Voutilainen
Keyword(s):  
Growth Factor ◽  
Cyclic Amp ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Α ◽  
Factor Ii ◽  
Epidermal Growth ◽  
Insulin Mrna ◽  
Igf Receptor ◽  
Factor Α

ABSTRACT To understand the development of the human pancreas better, we studied the expression and regulation of insulin, insulin-like growth factor-II (IGF-II) and transforming growth factor-α (TGF-α) genes in the human fetal pancreas and islet-like cell clusters (ICC) from the second trimester human fetuses. Northern blot analysis revealed an abundant expression of IGF-II, insulin and TGF-α mRNAs in the intact pancreas and the cultured ICCs. Furthermore, transcripts for insulin receptor, type-1 and -2 IGF receptors, and GH receptor could be amplified by polymerase chain reaction analysis from the pancreas and the ICCs. With in-situ hybridization, IGF-II mRNA was found in abundance in both the exocrine and endocrine pancreas, exceeding the amount of insulin mRNA. In ICCs, insulin mRNA-containing cells were present as small clusters in the periphery and in the centre of the clusters corresponding to the immunolocation of insulin. The ICCs also contained many epidermal growth factor-, insulin- and type-1 IGF receptor- and TGF-α-positive cells. When the ICCs were cultured in the presence of various secretagogues, only dibutyryl cyclic AMP was found to up-regulate insulin mRNA (39%; P < 0·05). IGF-II mRNA was also under cyclic AMP-dependent regulation (threefold increase; P = 0·025). Furthermore, blocking the type-1 IGF receptor with a monoclonal receptor antibody drastically reduced insulin expression (87%; P = 0·005) and additionally down-regulated IGF-II mRNA (49%; P = 0·005). IGF-1, IGF-II, TGF-α or epidermal growth factor-receptor antibody had no significant effect on either insulin or IGF-II mRNA. Exogenous TGF-α inhibited the release of insulin by the ICCs. It was concluded that IGF-II and TGF-α may be involved in the regulation of islet growth and differentiation. Journal of Endocrinology (1993) 138, 127–136

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