Insulin-like growth factor-I signaling in human neuroblastoma cells

Kim, Bhumsoo; Golen, Cynthia M. van; Feldman, Eva L.

doi:10.1038/sj.onc.1206924

Cited by 71 publications

(68 citation statements)

References 66 publications

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“…After binding insulin, it undergoes autophosphorylation and subsequently tyrosine phosphorylates insulin receptor substrates, src homology 2 domain-containing and growth factor receptor bound-2 associated binder-1, each of which provides specific docking sites for other signaling molecules. These events lead to activation of phosphatidylinositol-3 (PI3) kinase (Kim et al, 2004). Because PI3 kinase activation is a well recognized consequence of insulin signaling, we determined whether IDE upregulation was through PI3 kinase activation.…”

Section: Insulin Induces Ide Upregulation In Primary Hippocampal Neuronsmentioning

confidence: 99%

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Zhao¹,

Teter²,

Morita³

et al. 2004

J. Neurosci.

289

188

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Insulin-degrading enzyme (IDE) is one of the proteins that has been demonstrated to play a key role in degrading ␤-amyloid (A␤) monomer in vitro and in vivo, raising the possibility of upregulating IDE as an approach to reduce A␤. Little is known, however, about the cellular and molecular regulation of IDE protein. Because one of the main functions of IDE is to degrade insulin, we hypothesized that there is a negative feedback mechanism whereby stimulation of insulin receptor-mediated signaling upregulates IDE to prevent chronic activation of the pathway. We show that treatment of primary hippocampal neurons with insulin increased IDE protein levels by ϳ25%. Insulin treatment also led to phosphatidylinositol-3 (PI3) kinase activation evidenced by Akt phosphorylation, which was blocked by PI3 kinase inhibitors, wortmannin and LY 294002. Inhibition of PI3 kinase abolished the IDE upregulation by insulin, indicating a causeeffect relationship between insulin signaling and IDE upregulation. Further support for this link was provided by the findings that deficient insulin signaling (decreased PI3 kinase subunit P85) was correlated with reduced IDE in Alzheimer's disease (AD) brains and in Tg2576 Swedish amyloid precursor protein transgenic mice fed a safflower oil-enriched ("Bad") diet used to accelerate pathogenesis. Consistent with IDE function in the degradation of A␤ monomer, the IDE decrease in the Bad diet-fed Tg2576 mice was associated with increased A␤ monomer levels. These in vitro and in vivo analyses validate the use of enhanced CNS insulin signaling as a potential strategy for AD intervention to correct the IDE defects occurring in AD.

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Section: Insulin Induces Ide Upregulation In Primary Hippocampal Neuronsmentioning

confidence: 99%

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Zhao¹,

Teter²,

Morita³

et al. 2004

J. Neurosci.

289

188

View full text Add to dashboard Cite

show abstract

“…The biological actions of the IGFs are mediated through specific cell membrane receptors designated as the IGF-I and IGF-II receptors (Sepp-Lorenzino 1998; Hawkes and Kar 2003;Kim et al 2004). Alterations of the IGF-I and IGF-II binding sites in the spinal cord of the patients with ALS would support their involvement in the pathology of ALS (Dore et al 1996;Chung et al 2003;Kar et al 2006).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Up-Regulation of Insulin-Like Growth Factor-II Receptor in Reactive Astrocytes in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Rats

Dagvajantsan

Akiyama

Warita

et al. 2008

Tohoku J. Exp. Med.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by selective motor neuron death. We developed a rat model of ALS expressing a human cytosolic copper-zinc superoxide dismutase (SOD1) transgene with two ALS-associated mutations: glycine to alanine at position 93 (G93A) and histidine to arginine at position 46 (H46R). Although the mechanism of ALS is still unclear, there are many hypotheses concerning its cause, including loss of neurotrophic support to motor neurons. Recent evidence suggests that insulin-like growth factors (IGFs) act as neurotrophic factors, and promote the survival and differentiation of neuronal cells including motor neurons. Their ability to enhance the outgrowth of spinal motor neurons suggests their potential as a therapeutic agent for the patients with ALS. In this study, we investigated IGF-II receptor immunoreactivity in the anterior horns of the lumbar level of the spinal cord in SOD1 transgenic rats with the H46R mutation of different ages as well as in normal littermates. The double-immunostaining for IGF-II receptor and glial fibrillary acidic protein (GFAP) demonstrated colocalization on reactive astrocytes (**p < 0.001) in the end-stage transgenic rats, whereas it was not evident at the pre-symptomatic stage or at the onset of the disease. Our results demonstrated the IGF-II receptor up-regulation in reactive astrocytes in the spinal cord of transgenic rats, which may reflect a protective response against the loss of IGFrelated trophic factors. We suggest that IGF receptors may play a key role in the pathogenesis, and may have therapeutic implications in ALS.amyotrophic lateral sclerosis; insulin-like growth factor; transgenic rat; IGF receptor; SOD1 Tohoku

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“…The activated IGF-1 receptor phosphorylates docking proteins, which in turn activate downstream signaling proteins leading to diverse biological responses. PI3K and MAPK are two key enzymes that are activated by IGF-1; each represents a distinct signaling pathway that mediates the biological functions of IGF-1 (19). We therefore investigated the roles of PI3K and MAPK pathways in KCC production in response to IGF-1 stimulation.…”

Section: Igf-1 Increased Kcc Mrna Levels In a Concentration-and Time-mentioning

confidence: 99%

Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells

Shen¹,

Lin²,

Hsu³

et al. 2004

Journal of Biological Chemistry

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The mechanisms by which insulin-like growth factor 1 (IGF-1) cooperates with membrane ion transport system to modulate epithelial cell motility and proliferation remain poorly understood. Here, we investigated the role of electroneutral KCl cotransport (KCC), in IGF-1-dependent invasiveness and proliferation of cervical and ovarian cancer cells. IGF-1 increased KCC activity and mRNA expression in a dose-and time-dependent manner in parallel with the enhancement of regulatory volume decrease. IGF-1 treatment triggers phosphatidylinositol 3-kinase and mitogen-activated protein kinase cascades leading to the activation of Akt and extracellular signal-regulated kinase1/2 (Erk1/2), respectively. The activated Erk1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways are differentially required for IGF-1-stimulated biosynthesis of KCC polypeptides. Specific reduction of Erk1/2 protein levels with small interference RNA abolishes IGF-1-stimulated KCC activity. Pharmacological inhibition and genetic modification of KCC activity demonstrate that KCC is necessary for IGF-1-induced cancer cell invasiveness and proliferation. IGF-1 and KCC colocalize in the surgical specimens of cervical cancer (n ‫؍‬ 28) and ovarian cancer (n ‫؍‬ 35), suggesting autocrine or paracrine IGF-1 stimulation of KCC production. Taken together, our results indicate that KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers.

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Insulin-like growth factor-I signaling in human neuroblastoma cells

Cited by 71 publications

References 66 publications

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Insulin-Degrading Enzyme as a Downstream Target of Insulin Receptor Signaling Cascade: Implications for Alzheimer's Disease Intervention

Up-Regulation of Insulin-Like Growth Factor-II Receptor in Reactive Astrocytes in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Rats

Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells

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