• Development and Reproduction
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• 제3권1호
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• pp.69-74
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• 1999

Insulin-like growth factors (IGF-1 and IGF-2) play an important regulatory role in premplantation embryonic development. To study the role of IGF-1 during premplantation embryonic development in mouse, the presence of mRNA transcripts for IGF-1 and IGF-lR in the oocytes and preimplantation embryos was examined. In this study, the transcripts of IGF-1 was detected in oocytes using primers for IGF-1. The PCR products were identified by Msp I restriction enzyme digest. We revealed that the transcripts of IGF-1 and IGF-1R were presented in the oocytes and preimplantation embryos. The highest mRNA levels in GV stage oocytes were decreased at 4- or 8-cell stage and then reincreased upto blastocyst. The presence of IGF-1 and IGF-lR in GV-oocytes suggests that the transcripts in the early stage embryos were derived from maternal genome. Additionally, the presence of IGF-1 and IGF-lR in the oocytes and preimplantation embryos suggests that IGF-1 plays an autocrine role during preimplantation embryonic development through IGF-lR as a signalling pathway.

• Tuberculosis and Respiratory Diseases
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• 제63권1호
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• pp.42-51
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• 2007

Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). Results: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. Conclusion: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.

• Korean Journal of Animal Reproduction
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• 제27권1호
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• pp.1-7
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• 2003

Transgenic rabbits were produced by DNA microinjection using growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R) genes fused to metallothionein(MT) promoter. The overall efficiencies for production of transgenic rabbits were 3.2% and 3.1% for GHR and IGF-lR genes, respectively. Founder rabbits transmitted transgenes to their progenies through medelian fashion. Growth rate of GHR and IGF-lR transgenic rabbits was significantly faster than that of non-transgenic rabbits. Transgenic rabbits grew large. (25% and 15% increase in body weight of GHR and IGF-lR transgenic rabbits, respectively) than non-transgenic rabbits and organ weight of transgenic rabbits increased, suggesting that GHR and IGF-1R genes affects growth rates in transgenic rabbits.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.221-225
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• 2015

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether it can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

• Reproductive and Developmental Biology
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• 제30권2호
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• pp.93-97
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• 2006

To study the signaling effect of insulin-like growth factor-I(IGF-1), transgenic mice containing IGF-1 Receptor (IGF-1R) cDNA fused to metallothionein promoter were produced by DNA microinjection into the pronucleus of mouse zygote. Three founders were produced with transgenic mice containing IGF-1R gene. Transgenic mice lines contained approximately $4{\sim}20$ copies of transgenes per cell and transmission of this gene into the progeny with Mendelian manner were determined. The founder mice were mated with normal mice to produce $F_1$ mice and then $F_2$ mice. Transmission rates of IGF-1R transgene in the progeny mice were $25{\sim}60%$ in $F_1$ generation and $40{\sim}50%$ in $F_2$ generation. The mRNA expression of IGF-1R transgene in liver was analyzed using RT-PCR for IGF-1R gene in liver. When body weights of transgenic pups were measured during 4, 10 and 14 weeks after birth, IGF-1R transgenic mice grew faster than non transgenic littermates. This study indicated that growth regulation by IGF-1 signaling through IGF-1R can be elucidated using IGF-1R transgenic mice.

• Asian-Australasian Journal of Animal Sciences
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• 제33권10호
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• pp.1674-1682
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• 2020

Objective: This study aimed to elucidate the effect of miR-140 on the proliferation of porcine fetal fibroblasts (PFFs) and identify the target genes of miR-140 in PFFs. Methods: In this study, bioinformatics software was used to predict and verify target genes of miR-140. Quantitative polymerase chain reaction and western blot were used to detect the relationship between miR-140 and its target genes in PFFs. Dual luciferase reporter gene assays were performed to assess the interactions among miR-140, type 1 insulin-like growth factor receptor (IGF1R), and SRY-box 4 (SOX4). The effect of miR-140 on the proliferation of PFFs was measured by CCK-8 when PFFs were transfected with a miR-140 mimic or inhibitor. The transcription factor SOX4 binding to promoter of IGF1R was detected by chromatin immunoprecipitation assay (ChIP). Results: miR-140 directly targeted IGF1R and inhibited proliferation of PFFs. Meanwhile, miR-140 targeted transcription factor SOX4 that binds to promoter of porcine IGF1R to indirectly inhibit the expression of IGF1R. In addition, miR-140 inhibitor promoted PFFs proliferation, which is abrogated by SOX4 or IGF1R knockdown. Conclusion: miR-140 inhibited PFFs proliferation by directly targeting IGF1R and indirectly inhibiting IGF1R expression via SOX4, which play an important role in the development of porcine fetal.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 한국수정란이식학회 2000년도 추계학술대회 및 정기총회
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• pp.46-54
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• 2000

Transgenic rabbits were produced by DNA microinjection using growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R) genes. Overall efficiencies for production of transgenic rabbits were 3.2% and 3.1% in GHR and IGF-1R genes, respectively. Founder rabbits transmitted transgenes to their progenies through medelian fashion. Growth rate in GHR and ICF-1R transgenic rabbits was faster than non-transgenic rabbits. Transgenic rabbits grew larger (25% and 15% increase in body weight of GHR and IGF-1R transgenic rabbits, respectively) than non-transgenic rabbits and organ weight of transgenic rabbits increased, suggesting that GHR and IGF-1 genes affects growth rates in transgenic rabbits.

• Journal of Nutrition and Health
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• 제35권5호
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• pp.524-530
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• 2002

To evaluate the role of obesity and nutrient intake on serum IGF-1 and serotonin levels in 80 elementary school children (aged 10. 8 yr, 47 boys, 33 girls), we investigated the anthropometric data and the nutrient intake by questionnaries including food daily record, and measured serum IGF-1 and serotonin using RIA and HPLC F-1050 respectively. We obtained the following results by obesity index (underweight-, normal-, obese group). The protein intake of normal group was higher than the others (p < 0.05). The underweight and obese groups had snacks more often than the normal group. The obese group preferred‘cookies’and‘fries’more than the other groups. The serum serotonin levels showed weak correlation with fat (r = 0.315, p < 0.01), fiber (${\gamma}$ = 0.280, p < 0.05) and energy intake (r = 0.242, p < 0.05), but no differences in anthropometric data by obesity index. The serum IGF-1 level was significantly correlated height (r = 0.649, p < 0.001), weight (r = 0.437, p < 0.001) and hip (r = 0.417, p < 0.001), but showed weak correlation with energy intake (r = 0.232, p < 0.05) and carbohydrate intake (r = 0.244, p < 0.05). In this study, we could see only partly correlation among the serum IGF-1 and serotonin and obesity and nutrient intake. Forker research is required into consideration of the essential role of these hormones during a growth period.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6139-6144
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• 2012

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5753-5757
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• 2014

Background: The purpose of this study is to determine whether the IGF1R expression has a prognostic role in non-small cell lung cancer. Materials and Methods: Forty-seven patients histopathologically diagnosed with small cell lung cancer upon bronchoscopic biopsy or resection materials were included in the study. IGF1R expression was examined via immunohistochemical methods. In samples, >10% staining were assessed as positive and ${\leq}10%$ as negative. Information about demographic datas and treatments was obtained by retrospective searches of patient files. Results: IGF1R expression was determined as positive in 38 (80.9%) and as negative in 9 (19.1%) patients. There was no significant relation between IGF1R expression and histological sub-type, local invasion, lymph node and metastasis status (p=0.842, p=0.437, 0.064, 0.447, respectively). There was also no correlation with IGF1R expression and survival (p=0.141). Conclusions: There are conflicting results between IGF1R and its prognostic effects in the various studies. It has been claimed in some studies it is not related to prognosis as in our study, and in some studies it has been claimed that it is a good prognostic factor whereas in some studies it has been claimed as being a factor for worse prognosis. We think that IGF1R expression in non-small cell lung carcinoma patients deserves further analysis, because of its potential prognostic and predictive roles.