Disease relevance of IGFBP3

• Insulin-like growth factor binding protein-3 (IGFBP-3) has been proposed to mediate the growth inhibitory effects of transforming growth factor (TGF)-beta in breast and prostate cancer cells [1].
• Hypoxia caused a significant increase in IGFBP-3 secretion in BPAEC but not in BAEC [2].
• In conclusion, we showed that conditions mimicking hyperinsulinemia, rather than high levels of IGFs, could regulate BREC growth and that the IGF-I analog, Des(1-3), even with reduced affinity for IGFBPs but in part capable of binding to IGFBP-3, significantly stimulated BRECs growth only at 10 nmol/L [3].
• Body weights and serum concentrations of ST, IGF-I, IGFBP-2, and IGFBP-3 were determined [4].
• We have examined the regulation of endothelial IGFBP-3 production by IGF-I and TGF-beta, two growth factors thought to play a major roles in the complications of diabetes mellitus [5].

High impact information on IGFBP3

• IGFBP3 alone had no effect on stromal cell proliferation [6].
• Dissociation of the IGF-I-IGFBP3 complex renders IGF-I available to bind to its receptor and stimulates cellular proliferation [6].
• We evaluated the potential for PSA to modulate the effects of IGF-I and IGFBP3 on the proliferation of human benign prostatic hyperplasia (BPH)-derived fibromuscular stromal cells in primary cultures [6].
• When IGF-binding protein-3 (an inhibitor of IGF-I bioactivity) was added in combination with 25 micro M celecoxib, enhanced growth inhibition was observed (approximately 60% decrease in cell viability) [7].
• The Madin Darby bovine kidney (MDBK) cell line was used to investigate the mechanisms underlying the cAMP regulation of insulin-like growth factor binding protein-3 (IGFBP-3) gene expression [8].

Biological context of IGFBP3

• Expression patterns for certain genes (e.g., IGFBP3, HNF4A, GPAM) revealed adaptations commencing well ahead of parturition, suggesting they are regulated by factors other than periparturient hormonal environment [9].
• Whereas cultured human fibroblasts may be suitable to study posttranscriptional regulation of IGFBP-3 availability, cultured bovine fibroblasts may provide a useful model system to probe the molecular mechanisms of IGFBP-3 gene expression and regulation by IGF-I [10].
• Northern blotting indicated that endogenous IGFBP-3 mRNA, which was undetectable in wild-type (WT) MDBK cells, was expressed in MDBKpMONBP-3 cells while the IGFBP-3 transgene did not appear to be expressed [11].
• The alterations in morphology and IGFBP-3 expression were irreversible, since MDBKpMONBP-3 cells failed to revert to the WT phenotype upon removal of MTX and dialyzed serum [11].
• These results demonstrate that IGFBP-3 protein and RNA are expressed predominantly during early diestrus in the bovine CL [12].

Anatomical context of IGFBP3

• The amount of IGFBP2 and IGFBP3 in follicular fluid increased [13].
• IGFBP3, EIF4B, and GSTM5 mRNA levels were positively correlated with blood serum total protein [9].
• Northern analysis of bovine fibroblast RNA hybridized with a specific bovine IGFBP-3 complementary DNA probe indicated a single 2.8-kilobase (kb) transcript readily detectable within 2 h in IGF-I- or insulin-treated, but not in untreated, cells [10].
• Both TGF-beta and exogenous IGFBP-3 inhibit DNA synthesis in Mv1 mink lung epithelial cells (CCL64) [1].
• In this study we examined the expression of messenger RNA (mRNA) encoding IGFBP-3 in cultured bovine and human fibroblasts, two cell lines that secrete IGFBP-3 under IGF-I control [10].

Associations of IGFBP3 with chemical compounds

• Induction of IGFBP-3 mRNA was blocked when RNA synthesis was inhibited by actinomycin D [10].
• Enhanced expression of dihydrofolate reductase by bovine kidney epithelial cells results in altered cell morphology, IGF-I responsiveness, and IGF binding protein-3 expression [11].
• Pretreatment with the PI3K inhibitor LY294002 or knockdown of p85 with small interfering RNA inhibited IGF-I or TGFalpha-stimulated IGFBP-3 expression [14].
• Concentrations of E2 were correlated negatively with each IGFBP (r = -0.4 to -0.8; P < 0.05) except IGFBP-3 [15].
• Appearance of both IGFBP-3 and lactoferrin in conditioned media of primary cultures of bovine mammary cells was stimulated by all trans retinoic acid (atRA) [16].

Physical interactions of IGFBP3

• The percentage of the total IGF-I binding activity attributed to IGFBP-3 was greater (p < 0.05) in myometrium, serum, and uterine fluid (> 50%) than in inter- (40%) and intracaruncular (37%) endometrium [17].
• IGFBP-3 binds to membrane proteins of bovine mammary tissue; an IGFBP-3 binding protein has been identified as bovine lactoferrin [16].

Regulatory relationships of IGFBP3

• However, the regulatory mechanisms responsible for IGF-induced increases in IGFBP-3 are unclear [10].
• Vascular endothelial growth factor and transforming growth factor-beta1 regulate the expression of insulin-like growth factor-binding protein-3, -4, and -5 in large vessel endothelial cells [18].
• The phosphorylation of Akt was inhibited in a dose-dependent manner when IGFBP-5 was added at varying concentrations and was also inhibited in the presence of IGFBP-3 [19].
• In all cultures of marrow from postmenopausal women, IL-1 beta suppressed IGFBP-3 secretion to either undetectable levels or levels between 11% and 35% of control [20].

Other interactions of IGFBP3

• In contrast to its effect in bovine fibroblasts, IGF-I had no significant effect on steady state levels of IGFBP-3 mRNA in cultured human fibroblasts [10].
• We demonstrated that GH reduces mRNA and protein expression of IGFBP-5 in BMECs, but it does not affect the expression of IGFBP-3 [19].
• Vascular endothelial growth factor inhibited IGFBP-3 mRNA (P < 0.01) and protein expression and increased IGFBP-5 mRNA (P < 0.001) and protein [18].
• The amounts of IGFBP-3 in conditioned media were relatively low under basal conditions when analyzed by ligand blotting with 125I-IGF-II, but were increased dramatically relative to serum-free controls by exposure to IGF-I (100 ng/ml) or IGF-II (100 ng/ml) for 24 h [21].
• In ligand blots IGFBP-3 and IGFBP-4 appeared as the most prominent species [22].

Analytical, diagnostic and therapeutic context of IGFBP3

• In situ hybridization indicated that IGFBP-1 mRNA was primarily localized in luminal epithelium of endometrium; IGFBP-2 mRNA was in luminal epithelium and dense stromal cells adjacent to endometrial epithelium; and IGFBP-3 mRNA was in vascular endothelial cells and was more prevalent in myometrium than in endometrium [17].
• Using specific antisera, immunoblotting showed that the 43,000 and 39,000 Mr bands were IGFBP-3 and the 34,000 Mr band was IGFBP-2 [23].
• Both E(2) and trenbolone increased (3)H-thymidine incorporation rate (1.5-times control levels, P < 0.001) in BSC cultures in media containing serum from which IGFBP-3 had been removed by anti-IGFBP-3 affinity chromatography [24].
• We investigated the effect of purified bovine IGFBP-3 on IGF-I binding and IGF-I stimulation of amino acid uptake and DNA synthesis in cultured bovine fibroblasts, a cell culture system highly suitable for these types of studies [25].
• The concentration of IGFBP-3 produced was assessed using ligand and western blotting and secretion of progesterone, oxytocin, IGF-I, PGF and PGE was evaluated using RIA/IRMA techniques [26].

References