Disease relevance of IGFBP7

• In the present study, we have generated recombinant human mac25 (rh-mac25) in a baculovirus expression system and assessed its affinity for IGFs and have evaluated the pattern of expression of the mac25 gene in human tissues [1].
• We have examined mac25/IGFBP-rP1 and 25.1 as potential molecular regulators in vitro of the NE-differentiation process in lung cancer [2].
• Neuroendocrine-like differentiation of non-small cell lung carcinoma cells: regulation by cAMP and the interaction of mac25/IGFBP-rP1 and 25.1 [2].
• OBJECTIVES: To determine by genetic association analysis whether the 4q functional candidate genes IGFBP7, ADAMTS3, and IL8 might encode for susceptibility to osteoarthritis (OA) [3].
• The methylation statuses of the IGFBP7 gene for breast tumor and normal tissue samples and for normal human blood cell samples were detected successfully by the two procedures [4].
• Our study is the first to provide detailed methylation profiles of the IGFBP7 5' CpG island and shows that hypermethylation of the CpG island in exon 1 of IGFBP7 is closely related to the absence of its expression in colon cancer cells [5].

Psychiatry related information on IGFBP7

• Confirmatory factor analysis and reliability analysis suggested strong PSF scale psychometric properties (alpha = .92) [6].

High impact information on IGFBP7

• Here we report gene transfer experiments showing that expression of PSF complementary DNA in the human lymphoblastoid cell line mutant 721.134 restores normal levels of surface HLA-A2 and -B5 [7].
• Based on experiments in mice, it is proposed that some proliferative disorders of the pluripotential haemopoietic stem cell or its progeny may result from the abnormal production and secretion of PSF by these cells themselves [8].
• We showed that steroid synthesis could also be activated in mouse steroidogenic adrenal cells by transfection with cDNA encoding either mVL30 RNA tracts that form a complex with PSF or a small interfering RNA (siRNA) that degrades PSF transcripts [9].
• CTGF, like mac25/IGFBP-7, specifically binds IGFs, although with relatively low affinity [10].
• We have recently demonstrated that the product of the mac25/IGFBP-7 gene, which shows significant conservation in the NH2 terminus, including an "IGFBP motif' (GCGCCXXC), exhibits low-affinity IGF binding [10].

Chemical compound and disease context of IGFBP7

• The mRNA expression for IGFBP-rP1 was lacking in DU145, LNCaP, ND-1, and PC-3 prostate cancer cell lines, and after demethylation (5-aza-dC treatment), the expression was restored suggesting that methylation inactivated IGFBP-rP1 expression in prostate cancer cells [11].
• IGFBP-rP1 expression may also be associated with fasting glucose level and the presence of diabetes mellitus [12].
• The effect of mild high-calcium diet or regular-calcium diet on urinary calcium excretion, urinary oxalate excretion, urinary calcium/creatinine ratio, urinary oxalate/creatinine ratio, and the probability of being a stone former (PSF) were studied in 85 patients with idiopathic urolithiasis [13].
• PSF was 35-fold and 28-fold more toxic to RPMI 8322 melanoma cells than melphalan and m-L-sarcolysin, respectively [14].
• The cytotoxicity of both PSF and m-L-sarcolysin to RPMI 8322 melanoma cells was potentiated by depletion of cellular glutathione [14].

Biological context of IGFBP7

• The deduced amino acid sequence of the human mac25 propeptide shares a 20-25% identity to human insulin-like growth factor-binding proteins (IGFBPs), suggesting that mac25 could be another member of the IGFBP family [1].
• These data indicate that SOX9 contributes to growth regulation by mac25 via inhibition of cell growth and promotion of differentiation [15].
• IGFBP-rP1 (also known as MAC25/angiomodulin/prostacyclin-stimulating factor and T1A12), regulates cellular proliferation, adhesion, and angiogenesis and stimulates prostacyclin synthesis [16].
• Quantitative PCR was used to access the methylation status of the NotI site just 5' to the coding region and the expression level of the mac25/igfbp-7 gene [17].
• An altered locus/spot (S130) was cloned and found to correspond to sequences in the 5' flanking region and 5' portion of the cDNA for the murine mac25/insulin-like growth factor binding protein-7 (Igfbp-7) gene [17].

Anatomical context of IGFBP7

• The mac25 cDNA was originally cloned from leptomeningial cells and subsequently reisolated through differential display as a sequence preferentially expressed in senescent human mammary epithelial cells [1].
• A high endothelial venule secretory protein, mac25/angiomodulin, interacts with multiple high endothelial venule-associated molecules including chemokines [18].
• An increase and sustained activation of adenosine 3',5'-cyclic monophosphate (cAMP) levels induced NE-like differentiation in NSCLC cell lines, and a concomitant increase in the expression of mac25/IGFBP-rP1 and 25.1 was observed during the cAMP-regulated differentiation of NCI-H157 cells, suggesting the involvement of these proteins [2].
• IGFBP-rP1 was readily detectable in serum, urine, amniotic fluid, and cerebrospinal fluid by immunoblot analysis [16].
• The monoclonal anti-IGFBP-rP1 antibodies also readily detected IGFBP-rP1 expression in human tissue sections, with preferential expression of IGFBP-rP1 in the microvascular endothelium associated with tumorigenesis [16].

Associations of IGFBP7 with chemical compounds

• Binding of 125I-IGF-I and 125I-IGF-II to rh-mac25 was demonstrated by Western ligand blotting after nondenaturing polyacrylamide gel electrophoresis and by affinity cross-linking with as little as 2 nM rh-mac25 [1].
• Although the proteolytic cleavage of IGFBP-rP1 decreased its heparin-binding activity, the cleaved form could bind syndecan-1 efficiently [19].
• This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment [20].
• Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid [21].
• These findings suggest that mac25 may be a downstream effector of retinoid chemoprevention in breast epithelial cells and that its tumor-suppressive role may involve a senescence pathway [21].

Physical interactions of IGFBP7

• In conclusion, mac25 specifically binds IGFs and constitutes a new member of the IGFBP family, IGFBP-7 [1].

Enzymatic interactions of IGFBP7

• Syndecan-1 was thought to be a cell surface receptor for both intact and cleaved IGFBP-rP1 forms [19].
• When the membrane fraction was separated by SDS/PAGE, the IGFBP-rP1-cleaving activity comigrated with matriptase [22].

Regulatory relationships of IGFBP7

• A pRb immunoprecipitation demonstrated more binding of E2F-1 to pRb in the high expressing IGFBP-rP1/mac25 clones than in control cells [23].
• The data suggest that IGFBP-rP1 is a tumour suppressor inactivated by DNA methylation in human lung cancer [24].
• Further analysis of RNA and protein expression in breast tumor cell lines and patient tissue samples revealed that: IGFBP-rP1 is down-regulated in invasive tumors whereas cyclin I protein is regulated by ubiquitination and is associated with ER-negative breast cancers [25].

Other interactions of IGFBP7

• Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II [1].
• Furthermore, the collective overexpression of mac25/IGFBP-rP1 and 25.1 in NSCLC cells induced NE-like differentiation as early as 6 h postinfection [2].
• The cleavage of IGFBP-rP1 led to an almost complete loss of both insulin/IGF-1-binding activity and insulin/IGF-1-dependent growth-stimulatory activity [19].
• Biochemical and histochemical analysis confirmed the identification of mac25 and DARC as novel markers of the HEVECs [26].
• Moreover, the penetrance of the ventralization phenotype is much higher when we inactivated simultaneously chd, nog1 and fstl2 [27].

Analytical, diagnostic and therapeutic context of IGFBP7

• Additionally, we have developed a noncompetitive sandwich-type immunoassay to quantitate the concentrations of IGFBP-rP1 in human serum [16].
• Our microarray results led us to explore further and to quantify a specific gene, insulin-like growth factor-binding protein-7 (IGFBP7), using real-time quantitative reverse transcriptase-polymerase chain reaction assays and immunohistochemical protein expression [28].
• We also found that IGFBP7 mRNA and protein were significantly underexpressed in psoriatic compared with normal epidermis, and that phototherapy significantly increased their expression [28].
• We transfected PC-3 cell lines with IGFBP-rP1 cDNA (PC-3-rP1) and Northern blotting confirmed mRNA transcript of IGFBP-rP1 in these PC-3-rP1 clones [11].
• In situ hybridization revealed IGFBP-rP1 mRNA expression was detected in the stroma and epithelium of benign prostatic hyperplasia tissues but was either weak or lost in prostate cancer tissues [11].

References