Gene Symbol: IGFBP-3
Description: insulin like growth factor binding protein 3
Alias: BP-53, IBP3, insulin-like growth factor-binding protein 3, IBP-3, IGF-binding protein 3, IGFBP-3, acid stable subunit of the 140 K IGF complex, binding protein 29, binding protein 53, growth hormone-dependent binding protein
Species: human
Products:     IGFBP-3

Top Publications

  1. Han J, Jogie Brahim S, Harada A, Oh Y. Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-κB signaling. Cancer Lett. 2011;307:200-10 pubmed publisher
    ..The use of IGFBP-3 as a cancer therapeutic with this distinctive suppression mechanism may offer alternate means to treat chemotherapy resistant tumors. ..
  2. Chan S, Twigg S, Firth S, Baxter R. Insulin-like growth factor binding protein-3 leads to insulin resistance in adipocytes. J Clin Endocrinol Metab. 2005;90:6588-95 pubmed
    ..Finally, we showed that IGFBP-3 inhibited insulin-stimulated glucose uptake in omental but not s.c. adipose tissue explants. IGFBP-3 may contribute to insulin resistance in adipocytes. ..
  3. Kaplan R, Petersen A, Chen M, Teumer A, Glazer N, Doring A, et al. A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3. Hum Mol Genet. 2011;20:1241-51 pubmed publisher
    ..These genetic loci deserve further investigation to elucidate the biological basis for the observed associations and clarify their possible role in IGF-mediated regulation of cell growth and metabolism. ..
  4. Tomii K, Tsukuda K, Toyooka S, Dote H, Hanafusa T, Asano H, et al. Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers. Int J Cancer. 2007;120:566-73 pubmed
    ..079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined. ..
  5. Thelen P, Burfeind P, Grzmil M, Voigt S, Ringert R, Hemmerlein B. cDNA microarray analysis with amplified RNA after isolation of intact cellular RNA from neoplastic and non-neoplastic prostate tissue separated by laser microdissections. Int J Oncol. 2004;24:1085-92 pubmed
    ..Taken together, we present a novel method for the isolation of intact RNA from laser microdissection-derived prostate cancer tissue useful for downstream applications of real-time RT-PCR and cDNA microarrays. ..
  6. Patel A, Cheng I, Canzian F, Le Marchand L, Thun M, Berg C, et al. IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3). PLoS ONE. 2008;3:e2578 pubmed publisher
    ..In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women. ..
  7. Morimoto L, Newcomb P, White E, Bigler J, Potter J. Insulin-like growth factor polymorphisms and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14:1204-11 pubmed
    ..01). The current study provides some support for a role of IGFs in colorectal cancer etiology, particularly in mediating the relationship of common risk factors (physical activity, BMI, and postmenopausal hormone use). ..
  8. Diorio C, Brisson J, Bérubé S, Pollak M. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev. 2008;17:880-8 pubmed publisher
  9. Kielczewski J, Hu P, Shaw L, Li Calzi S, Mames R, Gardiner T, et al. Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury. Am J Pathol. 2011;178:1517-28 pubmed publisher

More Information


  1. Su X, Colditz G, Willett W, Collins L, Schnitt S, Connolly J, et al. Genetic variation and circulating levels of IGF-I and IGFBP-3 in relation to risk of proliferative benign breast disease. Int J Cancer. 2010;126:180-90 pubmed publisher
    ..These results suggest that genetic variants and circulating levels of IGFBP-3 may play a role in the early stage of breast carcinogenesis. ..
  2. Slattery M, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat. 2007;104:197-209 pubmed
    ..Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern United States may be dependent on estrogen exposure and may differ by ethnicity. ..
  3. Santer F, Bacher N, Moser B, Morandell D, Ressler S, Firth S, et al. Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysis. Cancer Res. 2006;66:3024-33 pubmed
    ..Moreover, we show that IGFBP-3, if ectopically expressed in the nucleus, can induce apoptotic cell death. These results suggest that ubiquitin/proteasome-mediated proteolysis of IGFBP-3 may contribute to down-regulation of apoptosis. ..
  4. Vestey S, Perks C, Sen C, Calder C, Holly J, Winters Z. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome. Breast Cancer Res. 2005;7:R119-29 pubmed
  5. Martin J, Lin M, McGowan E, Baxter R. Potentiation of growth factor signaling by insulin-like growth factor-binding protein-3 in breast epithelial cells requires sphingosine kinase activity. J Biol Chem. 2009;284:25542-52 pubmed publisher
  6. Li L, Huang X, Huo K. IGFBP3 polymorphisms and risk of cancer: a meta-analysis. Mol Biol Rep. 2010;37:127-40 pubmed publisher
    ..Further large study combining both IGFBP3 A-202C and Gly32Ala SNPs on different types of cancer in different populations were needed to validate former results. ..
  7. Dar A, Majid S, Nosrati M, De Semir D, Federman S, Kashani Sabet M. Functional modulation of IGF-binding protein-3 expression in melanoma. J Invest Dermatol. 2010;130:2071-9 pubmed publisher
    ..Our study results indicate that silencing of IGFBP3 in melanoma is due to the methylation of its promoter, and that overexpression of IGFBP3 induces apoptosis and suppresses cell survival and growth. ..
  8. Tamimi R, Cox D, Kraft P, Pollak M, Haiman C, Cheng I, et al. Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study. Breast Cancer Res. 2007;9:R18 pubmed
    ..2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005). Common genetic variation in IGF1 is strongly associated with percentage mammographic density. ..
  9. Duggan C, Wang C, Neuhouser M, Xiao L, Smith A, Reding K, et al. Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer. Int J Cancer. 2013;132:1191-200 pubmed publisher
    ..In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts. ..
  10. Jenkins P, Khalaf S, Ogunkolade W, McCarthy K, David T, Hands R, et al. Differential expression of IGF-binding protein-3 in normal and malignant colon and its influence on apoptosis. Endocr Relat Cancer. 2005;12:891-901 pubmed
    ..These effects are mediated in part by the PI-3K pathway in contrast to the MAP kinase pathway used by IGF-I. ..
  11. Grimberg A, Coleman C, Burns T, Himelstein B, Koch C, Cohen P, et al. p53-Dependent and p53-independent induction of insulin-like growth factor binding protein-3 by deoxyribonucleic acid damage and hypoxia. J Clin Endocrinol Metab. 2005;90:3568-74 pubmed
    ..Because IGFBP-3 can inhibit growth and induce apoptosis in IGF-dependent and IGF-independent manners, its induction by DNA damage and hypoxia suggest IGFBP-3 plays a role in the physiologic protection against aberrant cell growth. ..
  12. Gribben L, Baxter R, Marsh D. Insulin-like growth factor binding protein-3 inhibits migration of endometrial cancer cells. Cancer Lett. 2012;317:41-8 pubmed publisher
    ..This study demonstrates that endogenous IGFBP-3 modulates adhesion-migration dynamics in EC cells, implying that it may be important in regulating metastasis in this disease. ..
  13. Oh S, Kim W, Lee O, Kang J, Woo J, Kim J, et al. Insulin-like growth factor binding protein-3 suppresses vascular endothelial growth factor expression and tumor angiogenesis in head and neck squamous cell carcinoma. Cancer Sci. 2012;103:1259-66 pubmed publisher
    ..Taken together, these results support the hypothesis that IGFBP-3 has anti-angiogenic activity in HNSCC, at least in part due to IGF-independent suppression of VEGF production from vascular endothelial cells and cancer cells. ..
  14. Sheen Chen S, Zhang H, Huang C, Tang R. Insulin-like growth factor-binding protein-3 in breast cancer: analysis with tissue microarray. Anticancer Res. 2009;29:1131-5 pubmed
    ..The preliminary results about IGFBP-3 expression in breast cancer are intriguing and require further evaluation. ..
  15. Bhattacharyya N, Pechhold K, Shahjee H, Zappala G, Elbi C, Raaka B, et al. Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. J Biol Chem. 2006;281:24588-601 pubmed
    ..These results indicate that IGFBP-3 can induce apoptosis in an IGF-independent manner without being secreted or concentrated in the nucleus. ..
  16. McGrath M, Lee I, Buring J, De Vivo I. Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk. Gynecol Oncol. 2011;120:174-8 pubmed publisher
    ..Genetic variation with IGFII and IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further research is needed. ..
  17. Chen W, Wang S, Tian T, Bai J, Hu Z, Xu Y, et al. Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet. 2009;17:1668-75 pubmed publisher
    ..001). In conclusion, circulating levels of IGF1, IGFBP3 and IGFBP3 A-202C play a crucial role in carcinogenesis and could serve as susceptibility biomarkers for cancer development. ..
  18. Xiang H, Liu L, Chu G, Wei S, Liu J, Xu Y, et al. Association between two functional polymorphisms of insulin-like growth factor binding protein 3 and colorectal cancer risk in a Chinese population. J Toxicol Environ Health A. 2009;72:706-11 pubmed publisher
    ..Data suggest that the exon 1 G2133C missense variant of IGFBP3 may be a susceptibility factor for colorectal cancer in Chinese subjects. Larger studies are warranted to validate our findings in a Chinese population. ..
  19. Slattery M, Samowitz W, Curtin K, Ma K, Hoffman M, Caan B, et al. Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2004;13:1206-14 pubmed
    ..These data suggest that the insulin-related pathway may be important in the etiology of colon cancer but not rectal cancer. ..
  20. Fowke J, Matthews C, Yu H, Cai Q, Cohen S, Buchowski M, et al. Racial differences in the association between body mass index and serum IGF1, IGF2, and IGFBP3. Endocr Relat Cancer. 2010;17:51-60 pubmed publisher
    ..The effects of obesity throughout life on the IGF axis and racial differences in breast cancer risk require study. ..
  21. Butt A, Martin J, Dickson K, McDougall F, Firth S, Baxter R. Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: the role of altered epidermal growth factor signaling. J Clin Endocrinol Metab. 2004;89:1950-6 pubmed
  22. Ren Z, Cai Q, Shu X, Cai H, Li C, Yu H, et al. Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women. Cancer Epidemiol Biomarkers Prev. 2004;13:1290-5 pubmed
    ..05). These results indicated that IGFBP3 polymorphisms may be associated with the level of blood IGFBP-3 protein and an increased risk of breast cancer. ..
  23. Qian B, Zheng H, Yu H, Chen K. Genotypes and phenotypes of IGF-I and IGFBP-3 in breast tumors among Chinese women. Breast Cancer Res Treat. 2011;130:217-26 pubmed publisher
  24. Zhang M, Hu Z, Huang J, Shu Y, Dai J, Jin G, et al. A 3'-untranslated region polymorphism in IGF1 predicts survival of non-small cell lung cancer in a Chinese population. Clin Cancer Res. 2010;16:1236-44 pubmed publisher
    ..028). Our findings suggest that rs5742714 in IGF1 may be a genetic modifier for NSCLC prognosis in this Chinese population, especially among patients with surgical operation. ..
  25. Friedrich N, Alte D, Volzke H, Spilcke Liss E, Ludemann J, Lerch M, et al. Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: results of the Study of Health in Pomerania (SHIP). Growth Horm IGF Res. 2008;18:228-37 pubmed
    Insulin-like growth factor I (IGF-1), which is mostly carried by IGF binding protein 3 (IGFBP-3), mediates endocrine actions of growth hormone and represents an important prognostic factor for systemic diseases...
  26. Graziano F, Ruzzo A, Canestrari E, Catalano V, Santini D, Galluccio N, et al. Host genetic variants in the IGF binding protein-3 impact on survival of patients with advanced gastric cancer treated with palliative chemotherapy. Pharmacogenomics. 2010;11:1247-56 pubmed publisher
    ..Genetic regulation of the IGFBP-3 impacts on survival of patients with advanced gastric cancer. This finding deserves additional studies because of its prognostic and therapeutic implications. ..
  27. Schairer C, McCarty C, Isaacs C, Sue L, Pollak M, Berg C, et al. Circulating insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 levels and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort. Horm Cancer. 2010;1:100-11 pubmed publisher
    ..Further research should emphasize larger studies, including pooled analyses, analyses by cancer subtype, improved exposure assessment, and possible mechanisms. ..
  28. Kaplan R, McGinn A, Pollak M, Kuller L, Strickler H, Rohan T, et al. Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke. J Clin Endocrinol Metab. 2007;92:1319-25 pubmed
    ..Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events. ..
  29. Al Zahrani A, Sandhu M, Luben R, Thompson D, Baynes C, Pooley K, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet. 2006;15:1-10 pubmed
    ..More specifically and consistent with experimental models, our data suggest that higher IGF1 levels may increase the risk of breast cancer but higher IGFBP3 levels may be protective. ..
  30. Deming S, Ren Z, Wen W, Shu X, Cai Q, Gao Y, et al. Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study. Breast Cancer Res Treat. 2007;104:309-19 pubmed
    ..Taken together, these data suggest that polymorphisms in the IGF-1R and IGFBP3 genes may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status. ..
  31. Cortes Sempere M, De Miguel M, Pernia O, Rodriguez C, de Castro Carpeno J, Nistal M, et al. IGFBP-3 methylation-derived deficiency mediates the resistance to cisplatin through the activation of the IGFIR/Akt pathway in non-small cell lung cancer. Oncogene. 2013;32:1274-83 pubmed publisher
    ..84 and 0.9, respectively, (P=0.0062). We present a biomarker test that could provide clinicians with a robust tool with which to decide on the use of CDDP, improving patient clinical outcomes. ..
  32. Canzian F, McKay J, Cleveland R, Dossus L, Biessy C, Rinaldi S, et al. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study. Br J Cancer. 2006;94:299-307 pubmed
    ..Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians. ..
  33. Kojima S, Mulholland D, Ettinger S, Fazli L, Nelson C, Gleave M. Differential regulation of IGFBP-3 by the androgen receptor in the lineage-related androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer models. Prostate. 2006;66:971-86 pubmed
    ..C4-2 cell survival in an androgen-depleted environment may be facilitated through differential resistance to the apoptotic effects elicited by IGFBP-3. ..
  34. Burrows C, Holly J, Laurence N, Vernon E, Carter J, Clark M, et al. Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes. Endocrinology. 2006;147:3484-500 pubmed
    ..In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes. ..
  35. Flanagan D, Holt R, Owens P, Cockington R, Moore V, Robinson J, et al. Gender differences in the insulin-like growth factor axis response to a glucose load. Acta Physiol (Oxf). 2006;187:371-8 pubmed
    ..321, P = 0.004) and IGF-I (r = 0.339 P = 0.002) in men but not women. Our data show that IGFBP-1, IGFBP-3 and IGF-I show acute changes following a glucose load and there are marked gender differences in these responses. ..
  36. Schildkraut J, Demark Wahnefried W, Wenham R, Grubber J, Jeffreys A, Grambow S, et al. IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer in Black and White men. Cancer Epidemiol Biomarkers Prev. 2005;14:403-8 pubmed
    ..Further research is needed to confirm these findings. ..
  37. Gigek C, Leal M, Lisboa L, Silva P, Chen E, Lima E, et al. Insulin-like growth factor binding protein-3 gene methylation and protein expression in gastric adenocarcinoma. Growth Horm IGF Res. 2010;20:234-8 pubmed publisher
    ..In summary, our study did not observe any influence of IGFBP-3 promoter methylation on protein expression. Moreover we propose that IGFBP-3 immunostaining in gastric tissue may be a useful marker for malignancy. ..
  38. Wagner K, Hemminki K, Israelsson E, Grzybowska E, Söderberg M, Pamula J, et al. Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer. Breast Cancer Res Treat. 2005;92:133-40 pubmed
    ..The interaction between the IGF-1 and its receptor is mainly regulated by a binding protein, IGFBP 3. We studied a CA repeat polymorphism 969 bp upstream of the transcription start site in the IGF-1 gene and an A-..
  39. Ibanez de Caceres I, Cortes Sempere M, Moratilla C, Machado Pinilla R, Rodriguez Fanjul V, Manguan Garcia C, et al. IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer. Oncogene. 2010;29:1681-90 pubmed publisher
  40. Faupel Badger J, Berrigan D, Ballard Barbash R, Potischman N. Anthropometric correlates of insulin-like growth factor 1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels by race/ethnicity and gender. Ann Epidemiol. 2009;19:841-9 pubmed publisher
  41. Slattery M, Baumgartner K, Byers T, Guiliano A, Sweeney C, Herrick J, et al. Genetic, anthropometric, and lifestyle factors associated with IGF-1 and IGFBP-3 levels in Hispanic and non-Hispanic white women. Cancer Causes Control. 2005;16:1147-57 pubmed
    ..These differences could be due to the combined effects of genetic and behavioral factors which could account for ethnic differences in the risk of breast cancer and other chronic diseases. ..
  42. Lee Y, Jogie Brahim S, Lee D, Han J, Harada A, Murphy L, et al. Insulin-like growth factor-binding protein-3 (IGFBP-3) blocks the effects of asthma by negatively regulating NF-?B signaling through IGFBP-3R-mediated activation of caspases. J Biol Chem. 2011;286:17898-909 pubmed publisher
    ..The IGFBP-3/IGFBP-3R system therefore plays a pivotal role in the pathogenesis of asthma and can serve as a newly identified potential therapeutic target for this debilitating disease. ..
  43. Lettre G, Butler J, Ardlie K, Hirschhorn J. Common genetic variation in eight genes of the GH/IGF1 axis does not contribute to adult height variation. Hum Genet. 2007;122:129-39 pubmed
  44. Jogie Brahim S, Feldman D, Oh Y. Unraveling insulin-like growth factor binding protein-3 actions in human disease. Endocr Rev. 2009;30:417-37 pubmed publisher
  45. Johansson M, McKay J, Rinaldi S, Wiklund F, Adami H, Gronberg H, et al. Genetic and plasma variation of insulin-like growth factor binding proteins in relation to prostate cancer incidence and survival. Prostate. 2009;69:1281-91 pubmed publisher
    ..0003), and among patients who had not been treated (P(trend-adjusted) = 0.02). Circulating levels of intact IGFBP3 measured after diagnosis is associated with increased risk of prostate cancer-specific death. ..
  46. Kim H, Ali O, Shim M, Lee K, Vuguin P, Muzumdar R, et al. Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo. Pediatr Res. 2007;61:159-64 pubmed
  47. Friedrich N, Haring R, Nauck M, Ludemann J, Rosskopf D, Spilcke Liss E, et al. Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations. J Clin Endocrinol Metab. 2009;94:1732-9 pubmed publisher
    ..31; 2.64)] and women [HR 1.63 (95% CI 0.96; 2.76)]. The present study found inverse associations between IGF-I or IGFBP-3 levels and mortality from all causes, CVD, or cancer in men and between IGFBP-3 and all-cause mortality in women. ..
  48. Birmann B, Tamimi R, Giovannucci E, Rosner B, Hunter D, Kraft P, et al. Insulin-like growth factor-1- and interleukin-6-related gene variation and risk of multiple myeloma. Cancer Epidemiol Biomarkers Prev. 2009;18:282-8 pubmed publisher
    ..Nonetheless, the data are consistent with the hypothesis that IGF-1- and IL-6-related gene variation influences susceptibility to multiple myeloma and warrant confirmation in larger populations. ..
  49. Lai J, Vesprini D, Zhang W, Yaffe M, Pollak M, Narod S. A polymorphic locus in the promoter region of the IGFBP3 gene is related to mammographic breast density. Cancer Epidemiol Biomarkers Prev. 2004;13:573-82 pubmed
    ..A high circulating level of insulin-like growth factor-I (IGF-I) and low IGF binding protein 3 (IGFBP-3) level have been associated with increased breast density in premenopausal women...
  50. Serin I, Tanriverdi F, Yilmaz M, Ozcelik B, Unluhizarci K. Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women. Gynecol Endocrinol. 2008;24:117-21 pubmed publisher
  51. Chun S, Chen F, Washburn J, Macdonald J, Innes K, Zhao R, et al. CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3. Oncogene. 2007;26:4725-9 pubmed
    ..These data demonstrate for the first time that (1) CDX2 can function as a transcriptional repressor, and (2) one mechanism by which CDX2 promotes anchorage-independent growth is by transcriptional repression of IGFBP-3. ..
  52. McIntosh J, Dennison G, Holly J, Jarrett C, Frankow A, Foulstone E, et al. IGFBP-3 can either inhibit or enhance EGF-mediated growth of breast epithelial cells dependent upon the presence of fibronectin. J Biol Chem. 2010;285:38788-800 pubmed publisher
    ..The levels of fibronectin and IGFBP-3 within breast tumors may determine their dependence on EGFR and their response to therapies targeting this receptor. ..
  53. Rajpathak S, He M, Sun Q, Kaplan R, Muzumdar R, Rohan T, et al. Insulin-like growth factor axis and risk of type 2 diabetes in women. Diabetes. 2012;61:2248-54 pubmed publisher
    ..05-6.06]; P trend < 0.05). Thus, this prospective study found strong associations of incident diabetes with baseline levels of three IGFBPs and free IGF-I, consistent with hypotheses that the IGF axis might influence diabetes risk. ..
  54. Lin M, Marzec K, Martin J, Baxter R. The role of insulin-like growth factor binding protein-3 in the breast cancer cell response to DNA-damaging agents. Oncogene. 2014;33:85-96 pubmed publisher
    ..This suggests the possibility of a therapeutic approach for sensitizing breast cancer to chemo- or radiotherapy by targeting the DNA repair function of IGFBP-3. ..
  55. Chang Y, Wang L, Suh Y, Mao L, Karpen S, Khuri F, et al. Mechanisms underlying lack of insulin-like growth factor-binding protein-3 expression in non-small-cell lung cancer. Oncogene. 2004;23:6569-80 pubmed
    ..Thus interference with Sp-1 transactivation by MeCP2 may contribute to the transcriptional defect of IGFBP-3 expression in NSCLC cells with methylated promoter. ..
  56. Jiang B, Zhang X, Du L, Wang Y, Liu D, Han C, et al. Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer. World J Gastroenterol. 2014;20:1608-13 pubmed publisher
    ..The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease. ..
  57. Schumacher F, Cheng I, Freedman M, Mucci L, Allen N, Pollak M, et al. A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians. Hum Mol Genet. 2010;19:3089-101 pubmed publisher
  58. Lam C, Chen M, Lacey S, Yang Q, Sullivan L, Xanthakis V, et al. Circulating insulin-like growth factor-1 and its binding protein-3: metabolic and genetic correlates in the community. Arterioscler Thromb Vasc Biol. 2010;30:1479-84 pubmed publisher
    ..Prospective studies are warranted to elucidate whether lower IGF-1 concentrations predict greater metabolic risk longitudinally. ..
  59. Terry K, Tworoger S, Gates M, Cramer D, Hankinson S. Common genetic variation in IGF1, IGFBP1 and IGFBP3 and ovarian cancer risk. Carcinogenesis. 2009;30:2042-6 pubmed publisher
    ..Of particular interest was the IGFBP3 SNP rs2270628, which was associated with both increased IGF1 plasma levels and higher ovarian cancer risk. ..
  60. 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. ..
  61. Massoner P, Colleselli D, Matscheski A, Pircher H, Geley S, Jansen Durr P, et al. Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility. Endocr Relat Cancer. 2009;16:795-808 pubmed publisher
    ..These newly described mechanisms of IGFBP-3 can be of importance for tumor progression and support a role of IGFBP-3 in therapeutic settings. ..
  62. Torng P, Lee Y, Huang C, Ye J, Lin Y, Chu Y, et al. Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma. Oncogene. 2008;27:2137-47 pubmed
    ..Our results provide evidence and indicate that IGFBP-3 plays an important role as an invasion-metastasis suppressor in ovarian EC...
  63. Hernandez W, Grenade C, Santos E, Bonilla C, Ahaghotu C, Kittles R. IGF-1 and IGFBP-3 gene variants influence on serum levels and prostate cancer risk in African-Americans. Carcinogenesis. 2007;28:2154-9 pubmed
    ..Our study adds clarity and further support to the previous findings, implicating serum IGFBP-3 levels and the IGFBP-3 -202 A/C SNP in prostate carcinogenesis. ..
  64. Cheng I, Penney K, Stram D, Le Marchand L, Giorgi E, Haiman C, et al. Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. 2006;15:1993-7 pubmed
    ..Our results suggest that common genetic variation in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast cancer susceptibility. ..
  65. Williams A, Smartt H, H Zadeh A, MacFarlane M, Paraskeva C, Collard T. Insulin-like growth factor binding protein 3 (IGFBP-3) potentiates TRAIL-induced apoptosis of human colorectal carcinoma cells through inhibition of NF-kappaB. Cell Death Differ. 2007;14:137-45 pubmed
    ..We propose that IGFBP-3 is a non-toxic NF-kappaB inhibitor, which could be used as an adjuvant in the treatment of colon cancer. ..
  66. Fletcher O, Gibson L, Johnson N, Altmann D, Holly J, Ashworth A, et al. Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:2-19 pubmed
    ..Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely. ..
  67. Kirman I, Whelan R, Jain S, Nielsen S, Seidelin J, Nielsen O. Insulin-like growth factor binding protein 3 in inflammatory bowel disease. Dig Dis Sci. 2005;50:780-4 pubmed
    ..The level of intact IGFBP-3 is decreased in IBD patients with moderate to severe disease activity. This decrease may be linked to altered IGFBP-3 production or to increased cleavage by proteases other than MMP-9. ..
  68. Feik E, Baierl A, Hieger B, Führlinger G, Pentz A, Stättner S, et al. Association of IGF1 and IGFBP3 polymorphisms with colorectal polyps and colorectal cancer risk. Cancer Causes Control. 2010;21:91-7 pubmed publisher
    ..39, 95% CI 1.01-1.90). Our results suggest that the SNP rs6214 of IGF1 could have an impact on developing colorectal cancer and colorectal polyps with villous elements. ..
  69. D Aloisio A, Schroeder J, North K, Poole C, West S, Travlos G, et al. IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women. Cancer Epidemiol Biomarkers Prev. 2009;18:954-66 pubmed publisher
    ..Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels. ..
  70. Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Kirkner G, Fuchs C, et al. IGFBP3 promoter methylation in colorectal cancer: relationship with microsatellite instability, CpG island methylator phenotype, and p53. Neoplasia. 2007;9:1091-8 pubmed
    ..Our data suggest complex relationship between global genomic/epigenomic phenomena (such as MSI/CIMP), single molecular events (e.g., IGFBP3 methylation, TP53 mutation, and TGFBR2 mutation), and the related pathways. ..
  71. Pechlivanis S, Wagner K, Chang Claude J, Hoffmeister M, Brenner H, Forsti A. Polymorphisms in the insulin like growth factor 1 and IGF binding protein 3 genes and risk of colorectal cancer. Cancer Detect Prev. 2007;31:408-16 pubmed
    ..Nor did the haplotypes of these genes affect the risk of CRC. Our study suggests no major role of the assessed genetic variation within the IGF1 and the IGFBP3 genes in CRC risk. ..
  72. Yi H, Kim S, Hwang P, Kim C, Yang D, Oh Y, et al. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells. Biochem Biophys Res Commun. 2005;330:760-7 pubmed