Expression of IGF-II, the IGF-II/Mannose-6-Phosphate Receptor and IGFBP-2 During Rat Embryogenesis

Pintar, John E.; Wood, Teresa L.; Streck, Randal D.; Havton, Leif A.; Rogler, Leslie E.; Hsu, Ming-Sing

doi:10.1007/978-1-4684-5949-4_29

Cited by 12 publications

(5 citation statements)

References 41 publications

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“…Lane 3 RT ± PCR products from control livers of an adult (Table 1, Group 1) or Lane 4 RT ± PCR from a 3 day old perinatal C57B16 animal. Exon 1, 2, 3, levels refer to products as illustrated in (a) BMI is the positive control in all tissues except the choroid plexus and leptomeninges of the brain within the ®rst few weeks after birth (Pintar et al, 1991;Pimentel, 1994). Our study used a metallothionine promoter driven TGFa transgene which is expressed in the liver, resulting in hepatocarcinogenesis with a latency of approximately 12 ± 18 months.…”

Section: Discussionmentioning

confidence: 99%

Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice

Harris

Rogler

1998

Oncogene

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The Insulin like growth factor 2 (IGF2) gene is expressed in several types of tumors in humans and mice and has been implicated as an important growth factor in tumor progression. IGF2 expression in the TGFa transgenic mice was analysed in liver and tumors from animals which also contained one or two functional IGF2 alleles. In a two by two mating experiment using transgenic mice containing either a TGFa transgene or a IGF2 gene knockout, we have investigated whether IGF2 imprinting is reversed during hepatocarcinogenesis and the consequences of IGF2 expression for tumor growth. We observed that: (1) 100% of the hepatocellular carcinomas expressed IGF2 (2) the normally imprinted maternal allele is active in the tumors in which the paternal allele is knocked out and (3) all three of the murine IGF2 promoters upstream of the reactivated maternal alleles are transcriptionally active in tumors. We also observed that the total tumor burden of animals with two wild type IGF-2 alleles (paternal and maternal) was the same as the tumor burden in animals which contained only a single reactivated maternal allele. The 100% incidence of reactivation of the imprinted maternal allele suggests that IGF2 expression is selected during murine hepatocarcinogenesis and can substitute for the paternal allele when it is inactivated.

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Section: Discussionmentioning

confidence: 99%

Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice

Harris

Rogler

1998

Oncogene

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“…In mouse and rat embryos they display specific temporal and spatial expression patterns (Baker et al 1993;Powell-Braxton et al 1993;Cerro et al 1993;Green et al 1994;Orlowski et al 1990;Pintar et al 1991;Schuller et al 1993;Streck et al 1992;Wood et al 1990Wood et al , 1992. Of note are the mRNA expression patterns of IGFBP-2 and -5, which often overlap or are in adjacent tissues (Green et al 1994;Schuller et al 1993).…”

Section: Introductionmentioning

confidence: 98%

Major components of the insulin-like growth factor axis are expressed early in chicken embryogenesis, with IGF binding protein ( IGFBP ) -5 expression subject to regulation by Sonic Hedgehog

Allan

Zannoni

McKinnell

et al. 2003

Anatomy and Embryology

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Using whole-mount in situ hybridisation techniques, we have examined the expression of major components of the insulin-like growth factor (IGF) axis in early development of the chicken embryo, including both IGF-I and -II, the type 1 IGF receptor ( IGFR), and two of the IGF binding proteins, ( IGFBP) -2 and -5. We report that these genes fall into two distinct groups with respect to expression pattern, with IGFBP-2 displaying broad overlap of mRNA expression with IGFR and IGF-I during early development, whereas the expression profile of IGFBP-5 most closely resembled that of IGF-II. Comparison between different stages revealed IGFBP-2 mRNA was detected as early as stage 3, whereas IGFBP-5 was first seen at stage 4. In addition, we detected expression domains of IGFBP-5, and to a lesser extent IGFBP-2, which did not overlap with either IGFR or IGF expression patterns. This could indicate IGF independent actions of the IGFBPs during early embryonic development. A striking observation concerning the expression profiles of both IGF-II and IGFBP-5 at early stages of chick embryogenesis is that both these genes are expressed asymmetrically in a pattern similar to that of Sonic Hedgehog (Shh). Furthermore, using cyclopamine, we have demonstrated that IGFBP-5 expression in the early embryo is regulated by Shh. Taken together, these results describe an important role for the IGF system in the very early stages of the developing chicken embryo, and imply that IGFBP-2 and -5 are fundamental developmental factors, with the latter involved in Shh signalling pathways.

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“…The L-terminal domain can be proteolyzed by proteases such as MMPs, PAPP-A, and cathepsin-D. 23 IGFBP2 is highly expressed in rapidly dividing cell populations and in regions directly adjacent to cell growth and differentiation, such as the ectoderm after early implantation, the ventricular zone of rostral neuroepithelium, and the apical ectoderm ridge as well as in progenitor cells of the spleen. 24 , 25 Many studies have also reported that IGFBP2 is a tumorigenic factor with key oncogenic functions in the vast majority of human cancers and is a viable therapeutic target. 26 In the present study, we found that compared with that in the serum of healthy participants, the expression of IGFBP2 was significantly increased in the serum of patients with acute exacerbation of COPD and thus may be involved in COPD.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Serum Proteins in Chronic Obstructive Pulmonary Disease Assessed Using Label-Free Proteomics and Bioinformatics Analyses

Li¹,

Zhao²,

Liu³

et al. 2022

COPD

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Purpose As a common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high morbidity and mortality. Current clinical therapies are not ideal and do not improve lung function or long-term life quality. It is very important to find new potential pathogenic mechanisms, biomarkers, and targets with therapeutic value in COPD. Methods Serum samples collected from acute exacerbation and stable COPD and healthy participants were analyzed using label-free liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins (DEPs) between two groups. Bioinformatics analyses were performed to determine the biological processes associated with those DEPs. Key proteins were validated by enzyme linked immunosorbent assay (ELISA). Results In total, 661 proteins were detected in serum from patients with COPD and healthy participants. Compared with healthy participants, patients with acute exacerbation of COPD had 45 DEPs, 13 were upregulated and 32 were downregulated; and patients with stable COPD had 79 DEPs, 18 were upregulated and 61 were downregulated. Gene Ontology functional annotation results indicated that the DEPs identified in patients with COPD were associated with the terms cellular anatomical entity, binding, and cellular process. Kyoto Encyclopedia of Genes and Genomes functional annotation analysis and the Clusters of Orthologous Genes database analysis indicated that the functions of these DEPs were primarily in signal transduction mechanisms and amino acid transport and metabolism. The ELISA results for three key proteins of IGFBP2, LRG1 and TAGLN were consistent with the LC-MS/MS results and the area under the receiver operating characteristic of the combined index was 0.893 (95% CI: 0.813, 0.974). Conclusion Our findings suggested pathogenic mechanisms underlying COPD stages and indicated three key proteins that may warrant further study as potential biomarkers for early diagnosis or prognosis of COPD or as therapeutic targets.

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Expression of IGF-II, the IGF-II/Mannose-6-Phosphate Receptor and IGFBP-2 During Rat Embryogenesis

Cited by 12 publications

References 41 publications

Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice

Reactivation of the maternally imprinted IGF2 allele in TGFα induced hepatocellular carcinomas in mice

Major components of the insulin-like growth factor axis are expressed early in chicken embryogenesis, with IGF binding protein ( IGFBP ) -5 expression subject to regulation by Sonic Hedgehog

Differential Expression of Serum Proteins in Chronic Obstructive Pulmonary Disease Assessed Using Label-Free Proteomics and Bioinformatics Analyses

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