• Journal of Genetic Medicine
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• 제2권1호
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• pp.41-47
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• 1998

Human uniparental gestations such as gynogenetic ovarian teratomas provide a model to evaluate the integrity of parent-specific gene expression - i.e. imprinting - in the absence of a complementary parental genetic contribution. The few imprinted genes characterized so far include the insulin-like growth factor-2 gene (IGF2) coding for a fetal growth factor and H19 gene whose normal function is unknown but it is likely to act as an mRNA. IGF2 is expressed by the paternal allele and H19 by the maternal allele. This reciprocal expression is quite interesting because both H19 and IGF2 genes are located close to each other on chromosome 11p15.5. In situ RNA hybridization analysis has shown variable expression of the H19 and IGF2 alleles according to the tissue origin in 11 teratomas. Especially, Skin, derivative of ectoderm, is expressed conspicuously. We examined imprinting of H19 and IGF2 in teratomas using PCR and RT-PCR of exonic polymorphism. H19 and IGF2 transcript could be expressed either biallelically or monoallelically in the teratomas. Biallelic expression (i.e., loss of imprinting) of IGF2 occurred in 5 out of 6 mature teratomas and 1 out of 1 immature teratoma. Biallelic expression of H19 occurred in 4 out of 10 mature teratomas and 1 out of 1 immature teratoma. Expression levels of H19 and IGF2 transcript using the semi-quantitative RT-PCR had no relation between monoallelic and biallelic expression. Moreover, IGF2 biallelic expression did not affect allele-specificity or levels of H19 expression. These results demonstrate that both genes, H19 and IGF2, can be imprinted, expressed and regulated independently and individually of each other in ovarian teratoma.

• 한국발생생물학회지:발생과생식
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• 제2권2호
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• pp.205-212
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• 1998

$Na^{+}$이온 비의존적으로 작동하는 포도당 수송체 (glucose transporter 1, Glut1)는 생쥐 배아의 세포막을 경계로 포도당을 수송하는 주요통로이다. 성장인자 가운데 insulin-like growth factor-I (IGF-I)은 생쥐배아에서 포도당의 유입을 증가시키는 것으로 알려져있으나 이러한 효과가 IGF-I 의한 Glut1의 전사조절 효과에 기인한 것인지는 알려져 있지 않다. 본 연구는 포도당과 IGF-I 생쥐의 착상전 배아 발생과 Glut1 발현에 미치는 영향을 조사함으로써 이들에 의한 배발생 조절기작을 이해하고자 시행하였다. 2-세포기 배아는 배양액내 pyruvate 존재하에 포도당의 유무와 관계없이 포배로 발생하였다. IGF-I은 2-세포기에서 체외 발생한 중기포배내 할구수를 유의하게 증가시켰다. 2-세포기부터 체외발생한 상실배의 Glut1 전사체의 양에는 배양액내 포도당의 유무에 따른 차이가 없었으며, IGF-I은 포도당과 무관하게 Glut1의 발현을 증가시켰다. 이러한 결과에서 상실기 생쥐배아의 경우 단순히 포도당의 결핍에 의해 Glut1의 발현이 전사수준에서 촉진되지 않으며, Glut1 발현의 증가는 IGF-I에 의한 배발생 촉진효과와 관련이 있는 것으로 사료된다.

• 대한수의학회지
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• 제34권3호
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• pp.457-463
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• 1994

Insulin-like growth factor-I(IGF-I) plays an important role in the regulation of mammalian and poultry growth. IGF-I has many actions in different tissues, which include metabolic, mitogenic, and differentiative actions. IGF-I induces insulin-like effects - such as increased cell glucose uptake and glycogen sysnthesis, however several physiological actions of IGF-I may not have been identified yet. In order to investigate the effect on growth in broiler chicken treated with exogenous insulin-like growth factor-I, 30 chickens were injected $50{\mu}g$ reconbinant human IGF- I (rhIGF- I ) per kg body weight as experimental group and 30 ckickens saline subcutanously as control, 3 times according to ages from 2 to 35 days. We established radioimmunoassay method by which we can measure chicken IGF- I (cIGF- I ) as in rhIGF- I assay. The results obtained were as follows; 1) The dilution curve showed in parallelism between rhIGF- I and cIGF- I in the Sep-pak $C_{18}$ cartridge plasma extracts. 2) The body weight of broiler chicken were significantly increased at 31 days($1,176.50{\pm}99.79g$) and 35 days($1,252.84{\pm}125.21g$) of age in treatment groups, compared with control group($1,011.88{\pm}40.22g,\;1,111.32{\pm}153.67g$). The liver and kidney weights on 35 days$(35.24{\pm}5.18g,\;11.05{\pm}1.47g)$ were significantly higher in rhIGF- I treated group than control group($30.95{\pm}4.04g,\;10.01{\pm}1.60g$) 3) The plasma concentration of IGF- l and total protein in rhIGF- I treated group were $58.17{\pm}1.69ng/ml$, $3.75{\pm}0.62g/dl$ respectively compared with control group $45.70{\pm}1.64ng/ml$, $2.32{\pm}0.53g/dl$. The results suggest that exogenous rhIGF- I increased total body weight, liver and kidney weights in broiler chicken, and it may increase IGF- I and total protein concentration in serum.

• 생명과학회지
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• 제9권5호
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• pp.504-509
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• 1999

The trend of organogenesis in Xenopus presumptive ectoderm was studied by combined dose of activin A and IGF-1(insulin-like growth factor-1). In reference study of Asashima and his colleagues, the inductive patterns of various organs were reported with activin, the potent mesoderm inducing factor. In present study, the inducing pattern was cleared with combined-dose of concentration 1-100 ng/ml activin A and IGF-1. In addition, the result from single treatment of activin A was compared with former study. As a result, eye was differentiated in 5-20% of explants at 10 and 50 ng/ml concentrative combination of activin A. Otic vesicle was appeared in the entire concentrative combination of IGF-1. Pronephric duct was induced 19-38% of explants at the concentration of activin A 100 ng/ml by adding IGF-1. The comparison of single treatment of activin A was showed some difference in dose-dependent inducing pattern.

• KSBB Journal
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• 제17권3호
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• pp.283-289
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• 2002

Insulin-like growth factor-I(IGF-I)은 성장호르몬의 여러 가지 성정촉진 작용을 매개하는 분열 유발성 폴리펩티드이며, 조직의 수선과 재생, 창상치유 및 골대사와 같은 과정들에서 중요한 역할을 하는 것으로 알려져 있고, 비교적 여러 조직에서 발현되고 있는 IGF-I 유전자의 전사조절에 대한 정확한 분자적 기전과 호르몬 및 대사 상태가 그것을 어떻게 조절하는지 아직 밝혀져 있지 않다. 쥐를 절삭시키므로써 대사 상태를 변조시켰을 때, 간 조직내 IGF-I mRNA의 발현에 미치는 절식의 영향을 살펴보기 위하여 solution hybridizatioon/RNase protection 방법으로 분석 하였다. IGF-I의 exon 1 및 exon 2에 의하여 encode된 tran-scripts 모두가 감소된 결과를 얻었고, 이러한 감소는 전사 수준에서 일어난 것으로 nuclear run-on 분석에 의하여 확인하였다. 또한 절식시킨 쥐에서 IGF-I mRNA의 양을 조절하는 cia-acting elements를 IGF-I 유전자의 5'-flanking 지역과 exon 1과 econ 2에서 밝히고자 절식시킨 쥐의 신선한 간조직에서 핵 추출물을 얻어 IGF-I의 여러 가지 DNA fragments와 반응시켜 DNase I protection 분석을 한 결과, IGF-I 유전자의 주요한 전사 개 시점으로부터 downstream에 있는 sequences가 절식으로 변조시킨 대사상태에서 IGF-I의 발현 조절에 중요하며 이곳에는 전사인자인 C/EBP family의 isoform들을 포함한 간조직에 풍부하게 존재하는 여러 전사인자들이 결합할 것으로 제안하였다.

• Nutrition Research and Practice
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• 제7권6호
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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.

• 한국가축번식학회지
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• 제22권1호
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• pp.89-94
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• 1998

A study was made to investigate the effects of concerning factors with IGF-I recovery on the final IGF-I concentration in the effluent and to establish recovery conditions of IGF-I using liquid emulsion membranes(LEM). D2EHPA was best carrier among Amberlite LA2, Aliquit 336 and D2EHPA for recovery rate of IGF-I. Recovery rate of IGF-I by D2EHPA volume in the oil phase was increased as increasing D2EHPA volume, and optimal volume of D2EHPA was 5% in this experiment. The recovery rate of IGF-I by D2EHPA was increased by the decreasing from pH 7 to pH 4 of external phase. Therefore, optimal pH value was 4.0. Optimal concentrations of sulfuric acid in internal phase, paraffin oil in oil phase and Span 80 for recovery rate of IGF-I were 0.1M, 2.0% and 5%, respectively, and optimal W/O rate was 2. These results suggested that optimal conditions for recovery of IGF-I were D2EHPA(5%) as carrier, pH 4.0, 0.1M sulfuric acid, 2% paraffin oil, 2.0 W/O rate and 5.0% Span 80.

• BMB Reports
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• 제52권6호
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• pp.385-390
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• 2019

Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway.

• 한국수정란이식학회:학술대회논문집
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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 Microbiology and Biotechnology
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• 제9권1호
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• pp.113-118
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• 1999

The insulin-like growth factor (IGF) is found in all vertebrates and its type-II molecule is regarded as a fundamental embryonic growth factor during development. We have firstly identified, in this study, a cDNA clone corresponding to IGF-II (flIGF-II) from the adult brain of the teleost, Paralichthys olivaceus. We also examined the tissue expression of flIGF-II in several adult tissues by RT-PCR. The flIGF-II cDNA contained a complete ORF consisting of 215 amino acids and one stop codon. Its molecular characteristics appear to be similar to the previously identified IGF-II molecules, in which a common primary structure exhibiting B, C, A, D, and E domains is evidently observed. This cDNA clone seems to be cleaved at $Ala_{52}$ for the $NH_2$-end signal peptide and appears to produce a 98 amino acid-long E-peptide from the $Arg^{118}$. The functional B-D domain regions, therefore, include 65 amino acids and is able to encode a 7.4-kDa protein. The most prominent structural difference between IGF-I and IGF-II was that the D domain of IGF-II exhibits a two-codon-deleted pattern compared to the 8 amino acid-containing IGF-I. The insulin family signature in the A domain and six cysteins forming three disulfide bridges between the B and A domains were evolutionary-conserved from teleosts to mammalian IGF-II. Interestingly, the E-peptide region appears to provide a distinct hallmark between teleosts in amino acid composition. The flIGF-II shows 85.1% of sequence identity to salmon and trout, 90.6% to tilapia, and 98.4% to perch in amino acid level. In tissue expressions of IGF-II, it is very likely that flIGF-II has a significant expression in the adult brain. However, liver seems to be the main source for IGF-II production, and relatively low signals were observed in the adult muscle and kidney. Taken together, it would be concluded that the functional region for IGF-II mRNA is highly similar in phylogeny and is evolutionary, conserved as a mediator for the growth of vertebrates.