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IGFBP3  -  insulin-like growth factor binding protein 3

Homo sapiens

Synonyms: BP-53, IBP-3, IBP3, IGF-binding protein 3, IGFBP-3, ...
 
 
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Disease relevance of IGFBP3

  • The IGFBP1, IGFBP3, and COL1A1 gene promoter regions were found to be frequently methylated in primary renal cell tumors, and further study will provide insight into the biology of the disease and facilitate translational studies in renal cancer [1].
  • Increased expression of IGFBP3 was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (12 of 15, 80% versus 10 of 24, 42%), as well as in lymph node (6 of 7, 86%) and liver (9 of 9, 100%) metastases [2].
  • Polymorphic variation at the -202 locus in IGFBP3: Influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk [3].
  • When transplant recipients with and without posttransplant erythrocytosis were compared, similar levels of IGF-I were found; however, the group with erythrocytosis had significantly elevated IGFBP1 and IGFBP3 [4].
  • No statistically significant associations between the IGFBP3 C allele and prostate cancer were noted for Blacks (adjusted OR, 2.3; 95% CI, 0.8-6.2) or Whites (OR, 1.0; 95% CI, 0.3-3.1) [5].
  • We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha [6].
  • These findings suggest that serum levels of IGFBP-3 (and possibly IGF-I) are associated with the rate of HIV disease progression in women and, more broadly, that interindividual heterogeneity in the IGF axis may influence HIV pathogenesis [7].
 

Psychiatry related information on IGFBP3

  • Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis [8].
  • Hispanic women had significantly lower levels of IGFBP-3 (mean=3764.3 mcg/ml) after adjusting for age, body size, physical activity, menopausal status, and dietary factors than non-Hispanic white women (mean = 4058.0 mcg/ml; p<0.01) [9].
  • For male former vs never smokers, there were no differences in mean IGF-I and IGFBP-3 concentrations, suggesting that smoking cessation is associated with normalisation of peptide concentrations [10].
  • Levels of IGF-1 and IGFBP-3 did not differ between women with PMS and control subjects, supporting the concept that PMS and endogenous depression are biologically distinct entities [11].
  • Alcohol consumption (40 g), however, did not influence plasma levels of TGF-1beta, IGF-I or IGFBP-3 in either of the two groups at the time frame applied [12].
 

High impact information on IGFBP3

 

Chemical compound and disease context of IGFBP3

 

Biological context of IGFBP3

  • Three genes (IGFBP1, IGFBP3, and COL1A1) showed promoter methylation in tumor DNA but were unmethylated in normal cell DNA [1].
  • We found a positive relation between age-adjusted IGFBP-3 levels and plasma retinol (14% difference in IGFBP-3 in top vs. bottom tertiles of retinol, p for trend < 0.001; Spearman correlation coefficient r = 0.25), which was similar across genotypes at the -202 IGFBP3 locus (interaction term, F = 0.10, p = 0.91) [3].
  • There is prior evidence that the action of antiproliferative agents such as retinoids and selective estrogen receptor modulators (SERMs) act in part by upregulating IGFBP3 gene expression [3].
  • As a consequence of this event, the entire IGL locus, less the first three Vlambda elements, is translocated to chromosome 7, whereas the three remaining Vlambda elements on the der(22) are juxtaposed with IGFBP3 and IGFBP1 [22].
  • At birth, when analyzed according to gestational age, serum GH levels were increased (p = 0.0001) and serum IGF-I and IGFBP3 levels were decreased (p = 0.0001) in IUGR as compared with normal neonates [23].
 

Anatomical context of IGFBP3

 

Associations of IGFBP3 with chemical compounds

  • We confirmed a relation between the -202 IGFBP3 polymorphism and IGFBP-3 serum levels and observed a positive correlation between circulating retinol levels and circulating IGFBP-3 levels, providing further evidence that retinoids may influence IGF physiology [3].
  • METHODS: Fasting serum IGF-1, IGFBP3, testosterone, estrone, and sex hormone binding globulin were analyzed in 48 women on hormone replacement (HRT) (unopposed oral estrogen, HRT+, 74.0 +/- 6 years), 135 women not on HRT (HRT-, 77.3 +/- 7 years), and 128 healthy men (men, ) [29].
  • LBM in men was positively related to IGF-1 (p = .02) and testosterone (p < .01), whereas LBM was associated with IGFBP3 (p = .04) and total fat (p < .001) in female HRT+ and total fat (p < .01) in HRT- women [29].
  • Poor growth during steroid treatment is associated with lower IGF1 and IGFBP3 levels [30].
  • Inhibitor studies and IGFBP-3 zymography have demonstrated that the 92-kDa IGFBP-3 protease belongs to the class of serine-dependent proteases [31].
  • Women with higher intakes of citrus fruit or dietary vitamin C tend to have higher plasma concentrations of IGF-I and lower plasma concentrations of IGFBP-3 [32].
  • Chromatin immunoprecipitation with anti-USF-1/-2 showed an enrichment of IGFBP3 promoter in insulin-treated cells compared with unstimulated cells [33].
 

Physical interactions of IGFBP3

  • The precise mechanism by which IGFBP-3 interacts with the TGF-beta receptor system remains to be established [34].
  • Western ligand blotting of column effluent samples revealed 37-/43-kDa IGFBP-3 primarily in the 150-kDa complex in serum and a marked reduction in the amount of the 37-/43-kDa IGFBP in PF [35].
  • Both glycosylated and nonglycosylated IGFBP-3 bound to FN with a K(d) of approximately 0.3 nmol/L [36].
  • In control subjects, 89.8 +/- 4.47% of serum total IGF-I and 77.3 +/- 9.4% of serum total IGF-II were bound to serum IGFBP-3 [37].
  • Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3 [38].
 

Enzymatic interactions of IGFBP3

 

Co-localisations of IGFBP3

 

Regulatory relationships of IGFBP3

  • In SCL-1 cells, IGF-I and IGF-II were virtually identical in stimulating a mean 200% increase in IGFBP-3 (n = 5 experiments) [45].
  • The mature UD expressed IGFBP-3 mRNA while the ampulla in contact with the MB lacked IGFBP-3 mRNA and expressed IGFBP-2 exclusively [46].
  • To determine the importance of ALS in regulating the molecular distribution of hIGFBP-3, hALS was coinjected [47].
  • Insulin-like growth factors (IGFs) reduce IGF-binding protein-4 (IGFBP-4) concentration and stimulate IGFBP-3 independently of IGF receptors in human fibroblasts and epidermal cells [45].
  • In contrast, EGF suppressed IGFBP-3 mRNA and protein expression through activation of MAPK in an EGFR-tyrosine kinase-dependent manner to restore the cellular response to IGF-I [48].
 

Other interactions of IGFBP3

  • The Mr 32,000 binding protein is similar in size to IGFB-1 and different from IGFBP-2 and IGFBP-3, but it does not cross-react with an antibody against IGFBP-1 [49].
  • The next two linkages are Cys7-Cys9 and Cys8-Cys10, which are analogous to those previously determined for IGFBP-3 and IGFBP-5 [50].
  • IGFBP3 Nde I and the IGF1 (CT)n markers were not associated with responsiveness to overfeeding [51].
  • In synovial fluid of patients with OA, IGF-I levels were elevated, whereas IGF-II was decreased, and the IGFBP-3 level was similar to the control value [52].
  • The proportion of IGF-I associated with IGFBP-3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF-I/IGFBP-2 complexes [53].
 

Analytical, diagnostic and therapeutic context of IGFBP3

  • RESULTS: Renal transplant recipients have significantly elevated serum of IGF-I and IGFBP3 compared to normal individuals [4].
  • We investigated the association of two polymorphisms (A-202C and G2133C) in the IGFBP3 gene with plasma IGF hormone levels among 887 randomly selected participants in the Multiethnic Cohort study [54].
  • MEASUREMENTS: In a cross-sectional study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured serum total and free IGF-I, IGFBP-1 and IGFBP3 levels and sex steroids [55].
  • BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, height standard deviation score [HSDS], and body mass index [BMI]) [56].
  • Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA [57].

References

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  2. Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Hansel, D.E., Rahman, A., House, M., Ashfaq, R., Berg, K., Yeo, C.J., Maitra, A. Clin. Cancer Res. (2004) [Pubmed]
  3. Polymorphic variation at the -202 locus in IGFBP3: Influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk. Schernhammer, E.S., Hankinson, S.E., Hunter, D.J., Blouin, M.J., Pollak, M.N. Int. J. Cancer (2003) [Pubmed]
  4. Erythrocytosis after renal transplantation represents an abnormality of insulin-like growth factor-I and its binding proteins. Brox, A.G., Mangel, J., Hanley, J.A., St Louis, G., Mongrain, S., Gagnon, R.F. Transplantation (1998) [Pubmed]
  5. IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer in Black and White men. Schildkraut, J.M., Demark-Wahnefried, W., Wenham, R.M., Grubber, J., Jeffreys, A.S., Grambow, S.C., Marks, J.R., Moorman, P.G., Hoyo, C., Ali, S., Walther, P.J. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  6. Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha. Zappala, G., Elbi, C., Edwards, J., Gorenstein, J., Rechler, M.M., Bhattacharyya, N. Endocrinology (2008) [Pubmed]
  7. Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women. Strickler, H.D., Fazzari, M., Kovacs, A., Isasi, C., Napolitano, L.A., Minkoff, H., Gange, S., Young, M., Sharp, G.B., Kaplan, R.C., Cohen, M., Gunter, M.J., Harris, T.G., Yu, H., Schoenbaum, E., Landay, A.L., Anastos, K. J. Infect. Dis. (2008) [Pubmed]
  8. Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis. Støving, R.K., Flyvbjerg, A., Frystyk, J., Fisker, S., Hangaard, J., Hansen-Nord, M., Hagen, C. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
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  19. Insulin-like growth factor binding protein 3 mediates retinoic acid- and transforming growth factor beta2-induced growth inhibition in human breast cancer cells. Gucev, Z.S., Oh, Y., Kelley, K.M., Rosenfeld, R.G. Cancer Res. (1996) [Pubmed]
  20. Regulation of the insulin-like growth factors and their binding proteins by glucocorticoid and growth hormone in nonislet cell tumor hypoglycemia. Baxter, R.C., Holman, S.R., Corbould, A., Stranks, S., Ho, P.J., Braund, W. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
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  24. Characterization of insulin-like growth factor binding proteins and regulation of IGFBP3 in human mesangial cells. Grellier, P., Sabbah, M., Fouqueray, B., Woodruff, K., Yee, D., Abboud, H.E., Abboud, S.L. Kidney Int. (1996) [Pubmed]
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  29. Serum Sex Hormones, IGF-1, and IGFBP3 Exert a Sexually Dimorphic Effect on Lean Body Mass in Aging. Waters, D.L., Yau, C.L., Montoya, G.D., Baumgartner, R.N. J. Gerontol. A Biol. Sci. Med. Sci. (2003) [Pubmed]
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  31. Interaction of insulin-like growth factor II (IGF-II) with multiple plasma proteins: high affinity binding of plasminogen to IGF-II and IGF-binding protein-3. Oesterreicher, S., Blum, W.F., Schmidt, B., Braulke, T., Kübler, B. J. Biol. Chem. (2005) [Pubmed]
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  33. Identification of upstream stimulatory factor binding sites in the human IGFBP3 promoter and potential implication of adjacent single-nucleotide polymorphisms and responsiveness to insulin. Paquette, J., Bessette, B., Ledru, E., Deal, C. Endocrinology (2007) [Pubmed]
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  38. Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3. Storch, S., Kübler, B., Höning, S., Ackmann, M., Zapf, J., Blum, W., Braulke, T. FEBS Lett. (2001) [Pubmed]
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