• Journal of Veterinary Science
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• v.22 no.6
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• pp.77.1-77.10
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• 2021

Background: Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. Objectives: This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. Methods: The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5-175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5-79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2-57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6-70.5]) in healthy dogs. Conclusions: The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.

• 대한예방의학회:학술대회논문집
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• 2004.10a
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• pp.34.1-34.1
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• 2004

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.47-53
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• 2008

Purpose : The serum levels of total insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 reflect endogenous growth hormone (GH) secretion in healthy children. Free form of IGF-I which is suggested to have more potent biological action than complex form of IGF-I. The aim of this study is to investigate the serum levels of free IGF-I and its clinical value in healthy children. Methods : Serum levels of total IGF-I and IGFBP-3 were determined in 494 healthy children (248 boys and 246 girls) by RIA and IRMA. Serum level of free IGF-I was determined in 206 healthy children (103 boys and 103 girls) by IRMA. Results : The free IGF-I level increased with age in both sex. The free IGF-I level increased continuously between 7 and 15 years of age in boys, but decrement was noted after 14 years of age in girls. Serum total IGF-I level also increased with age in similar pattern of that of free IGF-I. There were no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age in both sex. And there were significant correlations between the level of free IGF-I and total IGF-I and the ratio of total IGF-I/IGFBP-3, respectively. Conclusion : In healthy children, serum free IGF-I increased with age in both sex and high free IGF-I level may play an important role in pubertal growth spurt. Our results suggest that the increased serum free IGF-I level in puberty may reflect changes in total IGF-I rather than IGFBP-3. But free IGF-I does not have more clinical value than total IGF-I because of no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age.

• Fisheries and Aquatic Sciences
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• v.22 no.9
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• pp.19.1-19.10
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• 2019

We investigated the insulin-like growth factor 1 (IGF-1)/AKT signaling pathway involved in muscle formation, growth, and movement in the adductor muscle of triploid Pacific oyster, Crassostrea gigas. Large and small triploid oysters (LTs and STs) cultured under identical conditions were screened, and the signaling pathways of individuals with superior growth were compared and analyzed. mRNA and protein expression levels of actin, troponin, tropomyosin, and myosin, proteins important in muscle formation, were higher in LTs compared with STs. Expression levels of IGF-1, IGF binding protein (IGFBP), and IGFBP complex acid-labile subunit were also higher in LTs compared with STs. Phosphorylation of the IGF receptor as well as that of AKT was high in LTs. In addition, the expression of phosphomammalian target of rapamycin and phospho-glycogen synthase kinase $3{\beta}$ was increased and the expression of Forkhead box O3 was decreased in LTs. Therefore, we suggested that the IGF-1/AKT signaling pathway affects the formation, growth, and movement of the adductor muscle in triploid oysters.

• Journal of Animal Science and Technology
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• v.57 no.9
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• pp.31.1-31.11
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• 2015

Background: This study was conducted to investigate the potential association of variation in the insulin-like growth factor binding protein 2 (IGFBP2) gene with growth, carcass and meat quality traits in pigs. IGFBP2 is a member of the insulin-like growth factor binding protein family that is involved in regulating growth, and it maps to a region of pig chromosome 15 containing significant quantitative trait loci that affect economically important trait phenotypes. Results: An IGFBP2 polymorphism was identified in the Michigan State University (MSU) Duroc ${\times}$ Pietrain $F_2$ resource population (n = 408), and pigs were genotyped by MspI PCR-RFLP. Subsequently, a Duroc pig population from the National Swine Registry, USA, (n = 326) was genotyped using an Illumina Golden Gate assay. The IGFBP2 genotypic frequencies among the MSU resource population pigs were 3.43, 47.06 and 49.51 % for the AA, AB and BB genotypes, respectively. The genotypic frequencies for the Duroc pigs were 9.82, 47.85, and 42.33 % for the AA, AB and BB genotypes, respectively. Genotype effects (P < 0.05) were found in the MSU resource population for backfat thickness at $10^{th}$ rib and last rib as determined by ultrasound at 10, 13, 16 and 19 weeks of age, ADG from 10 to 22 weeks of age, and age to reach 105 kg. A genotype effect (P < 0.05) was also found for off test Longissimus muscle area in the Duroc population. Significant effects of IGFBP2 genotype (P < 0.05) were found for drip loss, 24 h postmortem pH, pH decline from 45 min to 24 h postmortem, subjective color score, CIE $L^*$ and $b^*$, Warner-Bratzler shear force, and sensory panel scores for juiciness, tenderness, connective tissue and overall tenderness in MSU resource population pigs. Genotype effects (P < 0.05) were found for 45-min pH, CIE $L^*$ and color score in the Duroc population. Conclusions: Results of this study revealed associations of the IGFBP2 genotypes with growth, carcass and meat quality traits in pigs. The results indicate IGFBP2 as a potential candidate gene for growth rate, backfat thickness, loin muscle area and some pork quality traits.

• Molecules and Cells
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• v.42 no.4
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• pp.321-332
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• 2019

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

• Journal of Animal Science and Technology
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• v.50 no.2
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• pp.177-184
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• 2008

Acid-labile subunit(ALS) is a 85-kDa glycosylated plasma protein which forms a 150-kDa ternary complex with 7.5-kDa insulin-like growth factor(IGF) and 40~45-kDa IGF-binding protein-3. In a previous study, the present authors prepared a porcine ALS(pALS) expression construct by inserting a pALS coding sequence into a plasmid vector following synthesis of the sequence by reverse transcription-polymerase chain reaction(RT-PCR). The expression construct, however, was subsequently found to have a mis-sense mutation at two bases of the pALS coding sequence which is presumed to have occurred through a PCR error. In the present study, the correct coding sequence was synthesized by the site-directed mutagenesis and inserted into the pET-28a(+) plasmid expression vector containing the His-tag sequence flanking the last codon of the insert DNA. After induction of the expression construct in E. coli BL21(DE3) cells, the resulting presumptive recombinant peptide was purified by the Ni-affinity chromatography. Upon SDS- PAGE, the affinity-purified peptide was resolved as a single band at a 66-kDa position which is consistent with the expected molecular mass of the presumptive recombinant pALS. Collectively, results indicate that a recombinant pALS peptide was successfully expressed and purified in the present study.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Clinical and Experimental Pediatrics
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• v.48 no.3
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• pp.298-305
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• 2005

Purpose : We performed this study to evaluate the mean serum levels of insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein(IGFBP)-2 and IGFBP-3 in healthy Korean children according to age and sex. Methods : Ninety two healthy children, consisting of 42 boys and 50 girls, were classified into five groups according to age : neonate; infancy; early childhood; late childhood; and adolescence. We measured serum levels of IGF-I, IGFBP-2 and IGFBP-3 by enzyme-linked immunosorbent assay(ELISA) and analysed the serum levels according to sex and age group. Results : For boys, the mean serum levels of IGF-I(ng/mL) in neonate, infancy, early childhood, late childhood and adolescence were $41.1{\pm}3.6$, $70.9{\pm}33.7$, $103.5{\pm}97.2$, $89.8{\pm}46.5$ and $51.4{\pm}27.8$, respectively. Those of IGFBP-2(ng/mL) were $8.2{\pm}3.4$, $5.8{\pm}0.4$, $9.3{\pm}4.0$, $9.5{\pm}1.1$ and $7.0{\pm}0.5$, respectively. Those of IGFBP-3(ng/mL) were $559.2{\pm}215.2$, $1,333.3{\pm}692.5$, $2,254.6{\pm}1,513.8$, $2,447.1{\pm}1,464.2$, $1,533.6{\pm}807.4$, respectively. For girls, the mean serum levels of IGF-I(ng/mL) according to five age groups were $53.3{\pm}9.5$, $99.3{\pm}45.8$, $69.6{\pm}51.1$, $106.2{\pm}67.0$ and $145.1{\pm}127.8$, respectively. Those of IGFBP-2 (ng/mL) were $9.1{\pm}7.4$, $5.3{\pm}0.9$, $6.9{\pm}2.0$, $10.5{\pm}3.0$ and $7.9{\pm}1.3$, respectively. Those of IGFBP-3(ng/mL) were $858.2{\pm}433.4$, $1,834.8{\pm}851.3$, $1,404.3{\pm}570.2$, $2,203.5{\pm}899.4$ and $2,029.3{\pm}1,316.7$, respectively. There were significant positive correlations observed between IGF-I and IGFBP-3 levels(r=0.589, P=0.000). Conclusion : IGF-I and IGFBP-3 levels increased as children get older. The peak level of IGFBP-3 was observed in late childhood for both boys and girls, suggesting a current trend of children reaching peak growth velocity before adolescence. The IGFBP-2 level was higher in neonates compare to infancy, suggesting that IGFBP-2 is an important substance for fetal growth.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.8
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• pp.1180-1185
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• 2009

Two experiments were carried out to study the effects of dietary energy level on nutrient digestion, nitrogen (N) utilization, growth performance, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-3 (IGFBP-3) in plasma, liver and longissimus dorsi muscle in growing-finishing pigs. In experiment 1 (Exp 1), 15 castrated male pigs (Duroc${\times}$Landrace${\times}$Large White) (Body weight, BW, 55.6${\pm}$1.8 kg) were divided into three groups and fed rations containing 13.33, 14.87 and 17.35 MJ digestible energy (DE)/kg as treatments I, II and III, respectively, using soybean oil as an energy source. The experiment lasted 8 days and faecal and urinary samples were collected during the last 3 days. The results showed that the digestibility of dry matter (DM), energy and N was increased from treatments I to III (p<0.01). N-retention and N-retention rate were not influenced by dietary DE level (p>0.05). In experiment 2 (Exp 2), 36 female pigs (Duroc${\times}$Landrace${\times}$Large White) (BW 41.5${\pm}$3.8 kg) were divided into three groups. The pigs were fed with the same three rations used in Exp 1 for 60 days. At the end of Exp 2, eight pigs were selected from each group for blood sampling and 4 pigs for slaughter trial. The results indicated that average daily feed intake (ADFI) and N-intake were significantly decreased (p<0.01), and DE intake (p<0.01) and average daily gain (ADG) (p<0.05) were increased. IGF-I and IGFBP-3 in plasma were increased (p<0.05). No significant differences in IGF-I and IGFBP-3 in liver and longissimus dorsi muscle were found between different treatments. It was concluded that higher dietary DE level improved nutrient digestibility, ADG and feed/gain ratio when soybean oil was used as an energy source in the ration of growing-finishing pigs. No significant differences were found in Nretention and IGF-I and IGFBP-3 in liver and longissimus dorsi muscle between different treatments.