• Asian-Australasian Journal of Animal Sciences
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• v.18 no.11
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• pp.1575-1581
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• 2005

This study was conducted to determine the characteristics of IGFBPs in plasma of steers, and to profile the relationship between growth and plasma IGF-1 and IGFBPs with aging in Holstein steers. Four blots of IGFBP at molecular weights of 38-43, 34, 29-32 and 24 kDa bands were detected by western ligand blot assay using $^{125}I-IGF-1$. On the basis of immunoblotting with anti-bovine IGFBP-2 and -3 antiserums, we observed the band for IGFBP-2 at approximately 34 kDa, and the IGFBP-3 band was detected at 38-43 kDa and 34 kDa in adult steers and calves. The IGFBP-3 antiserum used on the blots exhibited significant cross-reactivity with 34 kDa IGFBP-2. Furthermore, the 38-43 kDa IGFBP-3 bands were reduced to a 36 kDa band after deglycosylation, whereas the 34 kDa IGFBP-2 was intact. The plasma IGF-1, IGFBP-3 and other IGFBPs showed stability throughout a whole day. The change in live weight was found to be positively correlated to the plasma IGF-1 concentration (r = 0.6801, n = 64, p<0.05) and plasma IGFBP-3 (r = 0.6321, n = 64, p<0.05), while inversely correlated to plasma IGFBP-2 (r = -0.2919, n = 64, p<0.05). Furthermore, plasma IGF-1 was positively correlated to plasma IGFBP-3 (r = 0.6191, p<0.001), but was not correlated to plasma IGFBP-2. The portion of IGFBP-2 for total IGFBPs in calves was higher than in adult steers (p<0.05) and was decreased with growth, whereas that of IGFBP-3 was increased with increased live weight (p<0.05). The ratio IGFBP-3 for IGFBP-2 (BP-3/BP-2) was increased with growing of liveweight. Therefore, the changes in plasma IGF-1 level with increased liveweight may be related to the changes in plasma IGFBP-3 level and IGFBP-2 may give an important role in anabolic action of IGF-1 with the growth of body during calfhood in Holstein steers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10181-10185
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• 2015

Background: MicroRNAs, small noncoding RNA molecules, can regulate mammalian cell growth, apoptosis and differentiation by controlling the expression of target genes. The aim of this study was to investigate the function of miR-323-5p in the glioma cell line, U251. Materials and Methods: After over-expression of miR-323-5p using miR-323-5p mimics, cell growth, apoptosis and migration were tested by MTT, flow cytometry and cell wound healing assay, respectively. We also assessed the influence of miR-323-5p on the mRNA expression of IGF-1R by quantitative real-time reverse transcriptase PCR (qRT-PCR), and on the protein levels by Western blot analysi. In addition, dual-luciferase reporter assays were performed to determine the target site of miR-323-5p to IGF-1R 3'UTR. Results: Our findings showed that over-expression of miR-323-5p could promote apoptosis of U251 and inhibit the proliferation and migration of the glioma cells. Conclusions: This study demonstrated that increased expression of miR-323-5p might be related to glioma progression, which indicates a potential role of miR-323-5p for clinical therapy.

• Journal of Life Science
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• v.28 no.2
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• pp.265-273
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• 2018

Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

• Journal of the korean academy of Pediatric Dentistry
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• v.50 no.3
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• pp.334-346
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• 2023

The aim of this study was to assess the correlation between serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and hand-wrist radiographs using a skeletal maturity indicator (SMI) and the middle phalanx of the third finger (MP3). Hand-wrist radiographs and blood samples from 205 patients aged 7 - 17 years were retrospectively analyzed by two dentists using the SMI stages, MP3 stages, and serum IGF-1 and IGFBP-3 levels. Serum IGF-1 levels were highest at the SMI 6 - 8 and MP3 - G stage and lowest at the SMI 1 - 3 and MP3 - F stage (p < 0.0001). Serum IGFBP-3 levels were highest at the SMI 9 - 10 and MP3 - I stage and lowest at the SMI 1 - 3 and MP3 - FG stage (p = 0.010, 0.030). As a result of Pearson correlation analysis, a relatively high correlation was found between skeletal maturity using the SMI and MP3 stages and serum IGF-1 levels (r = 0.698, 0.622, p < 0.0001). According to the results of this study, serum IGF-1 levels can be used as an auxiliary measure to evaluate the skeletal maturity of children and adolescents in dentistry. The range from the mean serum IGF-1 level of 472 ㎍/L in SMI 6 stage to the mean IGF-1 level of 510.63 ㎍/L in MP3 G stage could be considered as the peak height velocity in clinical practice.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3963-3969
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• 2016

Purpose:To assess IGFBP-6 expression in relation with the presence of the metabolic syndrome, adiponectin receptors (AdipoR1 and AdipoR2) and IGF-IR levels in colorectal adenocarcinoma cases. Materials and Methods: IGFBP-6 mRNA and protein levels were analyzed using real-time quantitative PCR and Western blotting in 46 patients. ELISA and flow cytometry were used for evaluation of AdipoR1, AdipoR2 and IGF-IR. Results: The results showed that IGFBP-6 mRNA expression and the IGFBP-6 content were higher in tumor tissue samples of colorectal cancer patients with tahtn without metabolic syndrome. In addition, the IGFBP-6 mRNA expression was associated with tumor invasion (tumor size) and the IGFBP-6 protein level was associated with nodal status. Positive correlations and positive nonlinear relations were found between the IGFBP-6 level and the AdipoR1 and AdipoR2 contents in colorectal cancer patients. Conclusions: The IGFBP-6 mRNA level and protein level were found to be associated with presence of metabolic syndrome. Positive correlations indicated probable cross-talk between the IGF-IR-mediated and adiponectin-mediated signaling pathways in colorectal carcinomas. IGFBP-6 may be considered as a potential biomarker associated with lymphogenous metastasis and the metabolic syndrome in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5675-5680
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• 2013

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

• Neonatal Medicine
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• v.15 no.1
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• pp.38-43
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• 2008

Purpose : The purpose of this study was to evaluate the relationship between cord serum adiponectin (APN) and IGF-I concentrations and fetal growth. Methods : Umbilical cord serum APN and IGF-I concentrations were measured in healthy term singleton deliveries (n=72). The association of cord serum APN and IGF-I concentrations was evaluated in relation to birth weight, height, head circumference, gender, ponderal index, placental weight, feto-placental (F/P) weight ratio, maternal weight gain, and maternal body mass index (BMI). Results : The mean cord serum APN was 29.2${\pm}$10.46 $\mu$g/mL. The cord serum APN and birth weight demonstrated a bell-shape relationship. The cord serum APN concentration was higher in females than males (P=0.001). The cord serum APN was negatively correlated with maternal BMI (r=-0.301, P=0.027), but the mean cord serum APN concentration was not correlated with birth height, birth head circumference, ponderal index, placental weight, F/P ratio, or maternal weight gain. The mean cord serum concentrations of IGF-I was 51.26${\pm}$21.54 ng/mL. The cord serum IGF-I concentration was positively correlated with birth weight (r=0.312, P=0.009), but not birth height, ponderal index, placental weight, F/P weight ratio, or maternal BMI. Conclusion : APN demonstrated a bell-shaped relationship with birth weight in healthy term infants. IGF-I was highly correlated with fetal growth, especially birth weight.

• 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.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.439-445
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• 2013

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

• Development and Reproduction
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• v.25 no.1
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• pp.67-72
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• 2021

This study investigated the IGF-1 signal in specific tissues using Pacific oysters artificially matured via water temperature elevation. Pacific oysters were subjected to water temperature elevation from March to June, and 20 were randomly sampled each month. The condition index (CI) and tissue weight rate (TWR) were examined by measuring shell length, shell height, shell width, and soft tissue weight. The IGF-1 signal in tissues (adductor muscle, digestive glands, gills, labial palps, mantle edges, and gonads) was analyzed by sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. From April to June, the TWR of females and males increased from 19.1±2.9 to 21.0±3.6 and 18.2±2.0 to 19.2±2.5, respectively, while the CI remained the same. The IGF-1 signal in each tissue differed. IGF-1 was expressed in the adductor muscle, while tyrosine was expressed in all tissues. The phosphor (p)-ERK and p-AKT activities were high in the adductor muscle, mantle edge, and gonads. IGF-1 signaling affected the growth and maturity of the Pacific oysters examined.