Genomes and Genes
insulin like growth factor binding protein 2
Summary: One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
- Hoeflich A, Wu M, Mohan S, Foll J, Wanke R, Froehlich T, et al. Overexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postnatal body weight gain. Endocrinology. 1999;140:5488-96 pubmed..05) lower in male transgenic than in control mice. Our data suggest that IGFBP-2 represents a negative regulator of postnatal growth in mice, potentially by reducing the bioavailability of IGF-I. ..
- Duan C, Ding J, Li Q, Tsai W, Pozios K. Insulin-like growth factor binding protein 2 is a growth inhibitory protein conserved in zebrafish. Proc Natl Acad Sci U S A. 1999;96:15274-9 pubmed..These results indicate that zebrafish IGFBP-2 is a negative growth regulator acting downstream in the growth hormone-IGF-I axis. ..
- DeMambro V, Clemmons D, Horton L, Bouxsein M, Wood T, Beamer W, et al. Gender-specific changes in bone turnover and skeletal architecture in igfbp-2-null mice. Endocrinology. 2008;149:2051-61 pubmed publisher..In summary, there are gender- and compartment-specific changes in Igfbp2(-/-) mice. IGFBP-2 may regulate bone turnover in both an IGF-I-dependent and -independent manner. ..
- Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, Kaku K, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008;57:791-5 pubmed..We have identified 6 of the 11 loci that were identified by genome-wide association studies in white populations, and these loci are considered strong candidates for type 2 diabetes susceptibility across different ethnicities. ..
- Neuvians T, Pfaffl M, Berisha B, Schams D. The mRNA expression of the members of the IGF-system in bovine corpus luteum during induced luteolysis. Domest Anim Endocrinol. 2003;25:359-72 pubmed..There were no significant changes in IGF I mRNA expression. In conclusion, the IGF-system with all its components seems to play an important role in the very complex process of PGF2alpha-induced luteolysis in bovine CL. ..
- Richardsen E, Ukkonen T, Bjørnsen T, Mortensen E, Egevad L, Busch C. Overexpression of IGBFB2 is a marker for malignant transformation in prostate epithelium. Virchows Arch. 2003;442:329-35 pubmed
- McMullen S, Osgerby J, Milne J, Wallace J, Wathes D. The effects of acute nutrient restriction in the mid-gestational ewe on maternal and fetal nutrient status, the expression of placental growth factors and fetal growth. Placenta. 2005;26:25-33 pubmed..This was accompanied by changes in placental VEGF and IGFBP expression. The growth of the fetal lung appears to have been compromised and this may have adverse consequences for subsequent neonatal respiratory function...
- Moore M, Wetterau L, Francis M, Peehl D, Cohen P. Novel stimulatory role for insulin-like growth factor binding protein-2 in prostate cancer cells. Int J Cancer. 2003;105:14-9 pubmed
- Babajko S, Grellier P, De Galle B, Menouny M, Binoux M. IGFBPs are involved in xenograft development in nude mice. Med Pediatr Oncol. 2001;36:154-6 pubmed..Although the mechanisms of action of IGFBP-2 and IGFBP-6 remain to be elucidated, an inverse relationship appears to exist between the two binding proteins, IGFBP-2 being involved in proliferation and IGFBP-6 in its arrest. ..
- Smink J, Koster J, Gresnigt M, Rooman R, Koedam J, Van Buul Offers S. IGF and IGF-binding protein expression in the growth plate of normal, dexamethasone-treated and human IGF-II transgenic mice. J Endocrinol. 2002;175:143-53 pubmed..In the growth plates of hIGF-II transgenic mice, the higher basal level of IGF-I, might be responsible for the observed partial protection against the adverse effects of GCs on bone. ..
- Grellier P, Berrebi D, Peuchmaur M, Babajko S. The IGF system in neuroblastoma xenografts: focus on IGF-binding protein-6. J Endocrinol. 2002;172:467-76 pubmed..This study therefore shows that IGFBP-6 plays a role in neuroblastoma cell growth in vivo and in vitro and that stable overexpression of IGFBP-6 leads to alteration of the initial balance between the IGFBPs. ..
- Wang H, Wang H, Shen W, Huang H, Hu L, Ramdas L, et al. Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res. 2003;63:4315-21 pubmed..Taken together, our data provide evidence that IGFBP2 contributes to glioma progression in part by enhancing MMP-2 gene transcription and in turn tumor cell invasion. ..
- Godard S, Getz G, Delorenzi M, Farmer P, Kobayashi H, Desbaillets I, et al. Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res. 2003;63:6613-25 pubmed..The separating groups of genes were found by the unsupervised coupled two-way clustering method, and their classification power was validated by a supervised construction of a nearly perfect glioma classifier. ..
- Pershing R, Lucy M, Thatcher W, Badinga L. Effects of BST on oviductal and uterine genes encoding components of the IGF system in lactating dairy cows. J Dairy Sci. 2002;85:3260-7 pubmed..Results indicate complex and tissue-specific regulation of the uterine IGF system components by exogenous bST. Some of those biological responses to bST may be important in early development of bovine embryos. ..
- Palermo C, Manduca P, Gazzerro E, Foppiani L, Segat D, Barreca A. Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity in differentiating osteoblasts. Am J Physiol Endocrinol Metab. 2004;286:E648-57 pubmed..These data suggest that IGFBP-2, at nearly equimolar concentration with IGF-II, plays a potentiating role in IGF-II action on ROB differentiation in vitro. ..
- Lancaster J, Dressman H, Whitaker R, Havrilesky L, Gray J, Marks J, et al. Gene expression patterns that characterize advanced stage serous ovarian cancers. J Soc Gynecol Investig. 2004;11:51-9 pubmed..With the generation of newer arrays with more transcripts, larger studies are possible to fully characterize genetic signatures that predict survival that may ultimately be used to guide therapeutic decision-making. ..
- Hoeflich A, Reisinger R, Vargas G, Elmlinger M, Schuett B, Jehle P, et al. Mutation of the RGD sequence does not affect plasma membrane association and growth inhibitory effects of elevated IGFBP-2 in vivo. FEBS Lett. 2002;523:63-7 pubmed..Our data demonstrate that in vivo IGFBP-2 cell surface association is not dependent on the RGD motif and that mutation of this sequence does not alter growth inhibitory effects of IGFBP-2. ..
- Baron Hay S, Boyle F, Ferrier A, Scott C. Elevated serum insulin-like growth factor binding protein-2 as a prognostic marker in patients with ovarian cancer. Clin Cancer Res. 2004;10:1796-806 pubmed..Identification of these patients at diagnosis may allow more individualized, aggressive adjuvant treatment and follow-up, and IGFBP-2 may therefore be an important additional prognostic marker in this disease. ..
- Schütt B, Langkamp M, Rauschnabel U, Ranke M, Elmlinger M. Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells. J Mol Endocrinol. 2004;32:859-68 pubmed..01). Since one of the cell lines used does not express a functional IGF-I receptor, these data demonstrate that IGFBP-2 can act in an IGF-independent manner, at least in part by an interaction with alpha5beta1-integrin. ..
- Reijnders C, Koster J, Van Buul Offers S. Overexpression of human IGF-II mRNA in the brain of transgenic mice modulates IGFBP-2 gene expression in the medulla oblongata. J Endocrinol. 2004;182:445-55 pubmed..In the medulla oblongata, the IGFBP-2 expression level showed 10-fold upregulation by the transgene, suggesting a modulating role for IGFBP-2 at the hIGF-II transgene action in this region. ..
- Wood A, Schlueter P, Duan C. Targeted knockdown of insulin-like growth factor binding protein-2 disrupts cardiovascular development in zebrafish embryos. Mol Endocrinol. 2005;19:1024-34 pubmed..These findings suggest that IGFBP-2 is required for general embryonic development and growth and plays a local role in regulating vascular development in a model vertebrate organism. ..
- Russo V, Schütt B, Andaloro E, Ymer S, Hoeflich A, Ranke M, et al. Insulin-like growth factor binding protein-2 binding to extracellular matrix plays a critical role in neuroblastoma cell proliferation, migration, and invasion. Endocrinology. 2005;146:4445-55 pubmed..Our novel findings thus point to a key role for the HBD of IGFBP-2 in the control and regulation of neuroblastoma growth and invasion. ..
- Wang G, Hu L, Fuller G, Zhang W. An interaction between insulin-like growth factor-binding protein 2 (IGFBP2) and integrin alpha5 is essential for IGFBP2-induced cell mobility. J Biol Chem. 2006;281:14085-91 pubmed..Therefore, we have concluded that one mechanism by which IGFBP2 activates IGFBP2-induced cell mobility is through its interaction with integrin alpha5 and this interaction is specifically mediated through the RGD domain on IGFBP2. ..
- Pereira J, Meyer T, Docherty S, Reid H, Marshall J, Thompson E, et al. Bimolecular interaction of insulin-like growth factor (IGF) binding protein-2 with alphavbeta3 negatively modulates IGF-I-mediated migration and tumor growth. Cancer Res. 2004;64:977-84 pubmed..Collectively, these results indicate that alpha v beta 3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells. ..
- Allander S, Illei P, Chen Y, Antonescu C, Bittner M, Ladanyi M, et al. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol. 2002;161:1587-95 pubmed
- Llewellyn S, Fitzpatrick R, Kenny D, Murphy J, Scaramuzzi R, Wathes D. Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows. Reproduction. 2007;133:627-39 pubmed
- Han V, Bassett N, Walton J, Challis J. The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab. 1996;81:2680-93 pubmed..Presumably, IGF-II and IGFBPs are used for cell to cell communication between fetal trophoblasts and maternal decidual cells at the feto-maternal interface for placental development and/or function. ..
- Smink J, Koster J, Hendriks Stegeman B, Van Buul Offers S. Insulin-like growth factor (IGF) II induced changes in expression of IGF binding proteins in lymphoid tissues of hIGF-II transgenic mice. Endocrinology. 1999;140:5876-82 pubmed..We speculate that an increase of IGFBP-3 expression together with changes in expression of other IGFBPs, inhibits IGF-II stimulated growth in the spleen by an autocrine-/paracrine pathway. ..
- Elmlinger M, Deininger M, Schuett B, Meyermann R, Duffner F, Grote E, et al. In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology. 2001;142:1652-8 pubmed..The results suggest cell type-specific accumulation of IGFBP-1, -2, and -3 in human glial tumors of the brain. The increase in IGFBP-2 expression with this malignancy suggests a role of IGFBP-2 in the biology of human gliomas. ..
- Wood T, Rogler L, Czick M, Schuller A, Pintar J. Selective alterations in organ sizes in mice with a targeted disruption of the insulin-like growth factor binding protein-2 gene. Mol Endocrinol. 2000;14:1472-82 pubmed..These results demonstrate that up-regulation of multiple IGFBPs accompanies the absence of IGFBP-2 and that IGFBP-2 has a critical role, either directly or indirectly, in modulating spleen and liver size. ..
- Hoeflich A, Fettscher O, Lahm H, Blum W, Kolb H, Engelhardt D, et al. Overexpression of insulin-like growth factor-binding protein-2 results in increased tumorigenic potential in Y-1 adrenocortical tumor cells. Cancer Res. 2000;60:834-8 pubmed..These data suggest that elevated levels of IGFBP-2 may contribute to the highly malignant phenotype of adrenocortical cancer by a thus far unknown, presumably IGF-independent, mechanism. ..
- Kanety H, Kattan M, Goldberg I, Kopolovic J, Ravia J, Menczer J, et al. Increased insulin-like growth factor binding protein-2 (IGFBP-2) gene expression and protein production lead to high IGFBP-2 content in malignant ovarian cyst fluid. Br J Cancer. 1996;73:1069-73 pubmed..This may represent an autocrine regulatory mechanism for IGF-I proliferative effect of ovarian cancer. ..
- Hilleson Gayne C, Clapper J. Effects of decreased estradiol-17beta on the serum and anterior pituitary IGF-I system in pigs. J Endocrinol. 2005;187:369-78 pubmed..These data further support a role for E2 in regulating components of the IGF system in pigs. ..
- Popovic V, Mattsson A, Gaillard R, Wilton P, Koltowska Haggstrom M, Ranke M. Serum insulin-like growth factor I (IGF-I), IGF-binding proteins 2 and 3, and the risk for development of malignancies in adults with growth hormone (GH) deficiency treated with GH: data from KIMS (Pfizer International Metabolic Database). J Clin Endocrinol Metab. 2010;95:4449-54 pubmed publisher..01)]. IGF-I levels targeted to within normal age-related reference ranges during GH replacement were not associated with the occurrence of malignancies. Higher IGFBP-2 and/or IGFBP-3 SDSs may be associated with increased cancer risk. ..
- Hastie P, Haresign W. Modulating peripheral gonadotrophin levels affects follicular expression of mRNAs encoding insulin-like growth factor binding proteins in sheep. Anim Reprod Sci. 2010;119:198-204 pubmed publisher..These data highlight that FSH and LH are involved, at least in part, in mediating the proliferative and differentiative changes in intrafollicular IGFBP levels that are observed during follicular growth and atresia in the sheep. ..
- Sim S, Chung Y, Jeong J, Yun S, Lim H, Kim D, et al. Immunohistochemical localization of insulin-like growth factor binding protein 2 in the central nervous system of SOD1(G93A) transgenic mice. J Mol Histol. 2009;40:157-63 pubmed publisher..This study showing decreased IGFBP2 in different brain regions of SOD1(G93A) transgenic mice may provide clues for understanding differential susceptibility of neural structures in ALS. ..
- Pang B, Zhang H, Wang J, Chen W, Li S, Shi Q, et al. Ubiquitous mitochondrial creatine kinase is overexpressed in the conditioned medium and the extract of LNCaP lineaged androgen independent cell lines and facilitates prostate cancer progression. Prostate. 2009;69:1176-87 pubmed publisher..Exogenous uMtCK in LNCaP cells surprisingly contributed to overproduction of ROS, activation of Akt signaling pathway and more aggressive phenotypes including androgen independence development. ..
- Zhou J, Li W, Kamei H, Duan C. Duplication of the IGFBP-2 gene in teleost fish: protein structure and functionality conservation and gene expression divergence. PLoS ONE. 2008;3:e3926 pubmed publisher..The duplicated IGFBP-2 genes may provide additional flexibility in the regulation of IGF activities. ..
- Hsieh T, Gordon R, Clemmons D, Busby W, Duan C. Regulation of vascular smooth muscle cell responses to insulin-like growth factor (IGF)-I by local IGF-binding proteins. J Biol Chem. 2003;278:42886-92 pubmed..IGFBP-5 not only modulates IGF-I actions, but it also stimulates cell migration by interacting with cell-surface heparan sulfate proteoglycans. ..
- Saleri R, Baratta M, Mainardi G, Renaville R, Giustina A, Quintavalla F, et al. IGF-I, IGFBP-2 and -3 but not GH concentrations are different in normal and poor growing piglets. Reprod Nutr Dev. 2001;41:163-72 pubmed..Piglet weight was positively correlated (r = 0.98, p < 0.001) with IGF-I and IGFBP-2 or -3 concentrations. Our data indicate that growth rate was not correlated to basal or secretagogue-induced GH secretion. ..
- Elias S, Keinan Boker L, Peeters P, van Gils C, Kaaks R, Grobbee D, et al. Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth factor axis. Int J Cancer. 2004;108:628-30 pubmed..These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine. ..
- Monaghan J, Godber I, Lawson N, Kaur M, Wark G, Teale D, et al. Longitudinal changes of insulin-like growth factors and their binding proteins throughout normal pregnancy. Ann Clin Biochem. 2004;41:220-6 pubmed..Our data on the physiological changes of IGFs and their binding proteins add further evidence of the vital roles of these hormones throughout normal pregnancy. ..
- Holmin S, Mathiesen T, Langmoen I, Sandberg Nordqvist A. Depolarization induces insulin-like growth factor binding protein-2 expression in vivo via NMDA receptor stimulation. Growth Horm IGF Res. 2001;11:399-406 pubmed..Taken together, these findings indicate that upregulation of IGFBP-2 by depolarization is mediated by NMDA receptors, and, as no neuronal damage was detected, astrocytic NMDA receptors may be responsible for this upregulation. ..
- Kiyama S, Morrison K, Zellweger T, Akbari M, Cox M, Yu D, et al. Castration-induced increases in insulin-like growth factor-binding protein 2 promotes proliferation of androgen-independent human prostate LNCaP tumors. Cancer Res. 2003;63:3575-84 pubmed..Inhibiting IGFBP-2 expression using ASO technology may offer a treatment strategy to delay AI progression. ..
- Corbo M, Lunetta C, Magni P, Dozio E, Ruscica M, Adobbati L, et al. Free insulin-like growth factor (IGF)-1 and IGF-binding proteins-2 and -3 in serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients. Eur J Neurol. 2010;17:398-404 pubmed publisher..Since IGF-1 is a trophic factor for different tissues, we speculate that high levels of the free IGF-1 in sALS might reflect a physiological defensive mechanism promoted in response to neural degeneration and/or muscle atrophy. ..
- Boersma B, Houwen R, Blum W, van Doorn J, Wit J. Catch-up growth and endocrine changes in childhood celiac disease. Endocrine changes during catch-up growth. Horm Res. 2002;58 Suppl 1:57-65 pubmed..Although several correlations between these endocrine alterations and auxological parameters were detected, it is questionable whether the endocrine changes are the driving force behind catch-up growth. ..
- Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K, et al. Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab. 2008;93:3136-41 pubmed publisher..Some of these variants represent common type 2 diabetes-susceptibility genes in both Japanese and Europeans. ..
- Simmen R, Zhang X, Michel F, Min S, Zhao G, Simmen F. Molecular markers of endometrial epithelial cell mitogenesis mediated by the Sp/Krüppel-like factor BTEB1. DNA Cell Biol. 2002;21:115-28 pubmed..Taken together, the results suggest that BTEB1 mediates the expression of growth-associated genes through direct and indirect transactivation mechanisms, one of which may involve the participation of a JNK family member. ..
- Kanaley J, Frystyk J, Møller N, Dall R, Chen J, Nielsen S, et al. The effect of submaximal exercise on immuno- and bioassayable IGF-I activity in patients with GH-deficiency and healthy subjects. Growth Horm IGF Res. 2005;15:283-90 pubmed..Thus the metabolic status during submaximal exercise does not require a change in plasma IGF-I bioavailability. Administration of GH to GHD adults does not result in changes in proteolysis or bioavailability. ..
- Fukushima T, Kataoka H. Roles of insulin-like growth factor binding protein-2 (IGFBP-2) in glioblastoma. Anticancer Res. 2007;27:3685-92 pubmed..However, it remains unclear how IGFBP-2 is involved in the malignant features of GBM. This review outlines the IGF-dependent and -independent functions of IGFBP-2 and focuses on the roles of IGFBP-2 in the progression of GBM. ..
- Frystyk J, Ivarsen P, Støving R, Dall R, Bek T, Hagen C, et al. Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay. Growth Horm IGF Res. 2001;11:117-27 pubmed..IRMA was less affected than UF by added IGFBP-1 and -2, and reductions in free IGF-I were better revealed by UF than IRMA. ..
- Levitt R, Georgescu M, Pollak M. PTEN-induction in U251 glioma cells decreases the expression of insulin-like growth factor binding protein-2. Biochem Biophys Res Commun. 2005;336:1056-61 pubmed..Our results motivate translational research regarding the relationship between IGFBP-2 expression and loss of function of PTEN. ..
- Thomas F, Campbell B, Armstrong D, Telfer E. Effects of IGF-I bioavailability on bovine preantral follicular development in vitro. Reproduction. 2007;133:1121-8 pubmed..In summary, the regulation of IGF-I bioavailability by IGFBPs is necessary for the co-ordination of oocyte and follicle development in vitro. ..
- Hausman G, Richardson R, Simmen F. Secretion of insulin-like growth factor (IGF)-I and -II and IGF binding proteins (IGFBPs) in fetal stromal-vascular (S-V) cell cultures obtained before and after the onset of adipogenesis in vivo. Growth Dev Aging. 2002;66:11-26 pubmed
- Maffei P, Boschetti M, Marshall J, Paisey R, Beck S, Resmini E, et al. Characterization of the IGF system in 15 patients with Alström syndrome. Clin Endocrinol (Oxf). 2007;66:269-75 pubmed..However, further tests, including GH dynamics, are needed to determine whether, or to what degree disturbances in the GH/IGF axis contribute to the relatively short stature. ..
- Sawai K, Kageyama S, Moriyasu S, Hirayama H, Minamihashi A, Onoe S. Changes in the mRNA transcripts of insulin-like growth factor ligand, receptors and binding proteins in bovine blastocysts and elongated embryos derived from somatic cell nuclear transfer. J Reprod Dev. 2007;53:77-86 pubmed..05) than in the Vivo embryos at the EL stage. These results suggest that there are differences in the levels and changes in the transcription of IGF-related genes in bovine embryos produced by NT-SC compared with those produced by Vivo. ..
- Vrieling A, Voskuil D, Bueno de Mesquita H, Kaaks R, van Noord P, Keinan Boker L, et al. Dietary determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1, -2 and -3 in women in the Netherlands. Cancer Causes Control. 2004;15:787-96 pubmed..Alcohol was inversely, and some measures of phytoestrogen intake were positively associated with plasma IGFBP-1 or -2 concentrations. The roles of IGFBP-1 and -2 in relation to IGF-I bioactivity and cancer deserve further investigation. ..
- Lukanova A, Lundin E, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, et al. Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy). Cancer Causes Control. 2003;14:285-92 pubmed..This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55. ..
- Espelund U, Bruun J, Richelsen B, Flyvbjerg A, Frystyk J. Pro- and mature IGF-II during diet-induced weight loss in obese subjects. Eur J Endocrinol. 2005;153:861-9 pubmed..This indicates a hitherto unrecognized link between nutrition and pro-IGF-II. In addition, our data indicate that pro-IGF-II is regulated independently of mature IGF-II. ..