Correlation of type I insulin-like growth factor receptor (IGF-I-R) and insulin receptor-related receptor (IRR) messenger RNA levels in tumor cell lines from pediatric tumors of neuronal origin

Elmlinger, Martin W.; Rauschnabel, Uta; Kościelniak, Ewa; Haenze, Jörg; Ranke, Michael B.; Berthold, A.; Klammt, J; Kieß, Wieland

doi:10.1016/s0167-0115(99)00065-8

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…Additionally, we also found suggestive association of UACl with SNPs in INSRR on chromosome 1. Some studies have suggested functional association between mRNA expression of insulin receptor-related and insulin-like growth factor receptors and tumor cells [40]. One GWAS study indicated a new locus linked to chromosome 2p22.1-p21 for familial juvenile hyperuricaemic nephropathy, [41] but none of our associations with urinary uric acid handling have been reported before.…”

Section: Discussionmentioning

confidence: 71%

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

et al. 2017

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BackgroundReduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study.MethodsWe performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members.ResultsAll renal urate excretion measures were significantly heritable (p <2 × 10−6) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10−7. We observed a strong association (p < 8 × 10−8) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10−6, MAFs: 0.28–0.31).ConclusionFor the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0366-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 71%

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

et al. 2017

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“…IRR also can form heterodimers with both the IR and IGF-1R (Kovacina and Roth, 1995;Jui et al, 1996). Recent work has demonstrated IRR expression, along with IGF-1R in a number of pediatric tumors of neuronal origin (Emlinger et al, 1999), possibly indicating a functional association.…”

Section: Discussionmentioning

confidence: 99%

BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons through Ras and PI‐3 kinase signaling

Kelly-Spratt

Klesse

Parada

2002

J of Neuroscience Research

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Insulin receptor-related receptor (IRR) expression is tightly coupled to the nerve growth factor (NGF) receptor, TrkA, throughout development. Expression of both receptors is primarily localized to neural crest derived sensory and sympathetic neurons. In contrast to TrkA, however, the physiological ligand for IRR is unknown. To analyze the intracellular signaling and potential function of the orphan IRR in neurons, an adenovirus expressing a TrkB/IRR chimeric receptor was used to infect cultured mouse superior cervical ganglion neurons that normally require NGF for survival. Brain derived neurotrophic factor (BDNF)-activated TrkB/IRR induced neuronal survival. We utilized numerous receptor mutants in order to identify the intracellular domains of IRR necessary for signaling and neuron survival. Finally, we employed adenovirus encoding dominant negative forms of the extracellular signal-regulated kinase (ERK) signaling cascade to demonstrate that IRR, like TrkA, requires ras activation to promote neuron survival. Therefore, by use of the chimeric TrkB/IRR receptor, we have demonstrated the ability of IRR to elicit activation of signaling cascades resulting in a biological response in superior cervical ganglion (SCG) neurons.

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“…The 12 soft tissue sarcoma (STS) cell lines used (table 1) were either purchased from the American Type Culture Collection (Rockville, Md., USA) or were established as primary cultures from biopsy material of the patients’ STS as described [17]. The 2 fibroblast cell lines GS-289 and GS-454 (kindly provided by Prof. Schweikert, Bonn, Germany) were obtained from foreskin biopsies of healthy boys after circumcision.…”

Section: Methodsmentioning

confidence: 99%

Secretion of Noncomplexed ‘Big’ (10–18 kD) Forms of Insulin-Like Growth Factor-II by 12 Soft Tissue Sarcoma Cell Lines

Elmlinger

Rauschnabel²,

Kościelniak³

et al. 1999

Horm Res Paediatr

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The paraneoplastic production of pro-insulin-like growth factor-II (IGF-II) forms causes tumour hypoglycaemias and presumably also has an effect on tumour cell growth. We investigated the molecular weights of IGF-II forms and their ability to form complexes with IGF binding proteins (IGFBPs) in conditioned culture media (CM) from 12 paediatric soft tissue sarcoma (STS) cell lines and from two healthy fibroblast lines. Untreated CM were separated by size exclusion chromatography using biocompatible HPLC. Subsequently, IGF-II, IGFBP-2 and IGFBP-3 were determined in the HPLC fractions by specific RIAs. In the CM, IGF-II concentrations between 0.5 and 8.6 ng/10⁶ cells were measured but no IGF-I was detectable. Parallel to this investigation, a high IGF-II mRNA level averaging 44.4 ± 29.7% was measured by semi-quantitative RT-PCR. The STS cell lines secreted a higher proportion of big-IGF-II forms reaching 10–18 kD (10–33% of the total IGF-II secreted) compared to the healthy fibroblasts (2.5–5%). At the same time, the proportion of IGF-II bound with IGFBP in complexes of 35– 70 kD and 150 kD was reduced by up to 85% in CM from tumour cells. The tumour cell lines apparently secrete a different spectrum of IGF-II forms than healthy fibroblasts. The reduced ability to form complexes with IGFBP and the higher molecular weight of the IGF-II forms produced by the tumour cells indicate that these forms could in fact be the known tumour-associated pro-IGF-II forms. Due to these characteristics, the big-IGF-II forms probably have an altered biological effect on the tumour cells when compared to IGF-II.

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Correlation of type I insulin-like growth factor receptor (IGF-I-R) and insulin receptor-related receptor (IRR) messenger RNA levels in tumor cell lines from pediatric tumors of neuronal origin

Cited by 7 publications

References 18 publications

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

BDNF activated TrkB/IRR receptor chimera promotes survival of sympathetic neurons through Ras and PI‐3 kinase signaling

Secretion of Noncomplexed ‘Big’ (10–18 kD) Forms of Insulin-Like Growth Factor-II by 12 Soft Tissue Sarcoma Cell Lines

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