Transgenic mouse models for studying the functions of insulin‐like growth factor‐binding proteins

Schneider, Marlon R.; Lahm, Harald; Wu, Minyao; Hoeflich, Andreas; Wolf, Eckhard

doi:10.1096/fasebj.14.5.629

Cited by 121 publications

(84 citation statements)

References 102 publications

(76 reference statements)

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“…The primary actions of IGFs are mediated through binding and activation of their cell surface receptors. Receptor-ligand interactions are regulated by a family of IGF-binding proteins (IGFBPs; Schneider et al, 2000). The mechanism by which IGFBPs regulate myoblast differentiation is not completely known.…”

Section: Genes Expressed Only During Early Myoblast Differentiation Cmentioning

confidence: 99%

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Shen

Collier

Hlaing

et al. 2002

Developmental Dynamics

105

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Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21 WAF1/Cip1 increased and ␣-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing ϳ10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation. Developmental Dynamics 226:128 -138, 2003.

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Section: Genes Expressed Only During Early Myoblast Differentiation Cmentioning

confidence: 99%

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Shen

Collier

Hlaing

et al. 2002

Developmental Dynamics

105

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“…IGF-1 functions by binding to its receptor (IGF-1R) and IGF-1 binding proteins (IGFBPs). To date, 6 members of the IGFBP family have been described (23). The binding of IGF-1 to IGF-1R may trigger the activation of several intracellular kinases, including PI3K (24,25).…”

Section: Introductionmentioning

confidence: 99%

IGF-1 activates the P13K/AKT signaling pathway via upregulation of secretory clusterin

Bai

2012

Molecular Medicine Reports

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Abstract. Secretory clusterin (sCLU) is a type of stressinduced, pro-survival glycoprotein elevated in early-stage cancer. It enhances cancer cell survival and is associated with several types of cancer progression. In this study, we measured the PI3K/AKT signaling activity by determining the phosphorylation level of the AKT protein, namely pAKT. A549 human non-small cell lung carcinoma (NSCLC) cells were treated with insulin-like growth factor-1 (IGF-1) for various periods of time.The results showed that IGF-1 activated the PI3K/AKT signaling pathway in the A549 cells in a time-dependent manner. Western blot analysis was performed to determine the expression of sCLU protein in A549 cells treated with IGF-1. IGF-1 elevated the expression of sCLU. To determine whether sCLU is required for the IGF-1 activation of the PI3K/AKT signaling pathway, the A549 cells were treated with IGF-1 and sCLU antisense oligonuleotide (sCLU ASO). sCLU ASO blocked the IGF-1 activation of the PI3K/AKT signaling pathway. These results demonstrate that IGF-1 activates the P13K/AKT signaling pathway via the upregulation of sCLU. The present study implies that this pathway may uncover a new mechanism for cancer progression and reveal new targets for drug development in the treatment of NSCLC.

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“…They were isolated from different tissues in several species and are characterised at the molecular level. Data obtained from several in vitro and in vivo experiments, and more recently also from transgenic animal models (Schneider et al 2000), indicate that the IGFBPs are far more than mere binding proteins. These highly conserved proteins are secreted in a tissue-and developmental stage-specific manner, they are present in different concentrations in different body compartments, they can modulate IGF bioactivity positively or negatively and they also exert IGF-independent effects (Kelley et al 1996, Rajaram et al 1997.…”

Section: Introductionmentioning

confidence: 99%

IGF-binding protein-5: flexible player in the IGF system and effector on its own

Schneider¹,

Wolf²,

Hoeflich³

et al. 2002

Journal of Endocrinology

160

137

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The multiple activities of IGF-I and -II are modulated by a family of IGF-binding proteins (IGFBP-1 to -6). Although structurally related, each IGFBP has unique properties and exerts specific functions. IGFBP-5 is the most conserved IGFBP across species and was identified as an essential regulator of physiological processes in bone, kidney and mammary gland. In addition, IGFBP-5 appears to play a decisive role in the control of proliferation of specific tumour cell types. In many situations IGFBP-5 exerts biological activities in the absence of IGFs, indicating the existence of IGF-independent actions. This concept was supported by the unexpected localisation of IGFBP-5 in the nucleus and the description of IGFBP-5-specific membrane-bound IGFBP-5 receptor(s). The scope of this review is to summarise the available information about the structure of IGFBP-5 and the regulation of its expression. Furthermore, the potential significance of IGFBP-5 in the regulation of physiological processes will be critically analysed in the light of recent experimental data.

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Transgenic mouse models for studying the functions of insulin‐like growth factor‐binding proteins

Cited by 121 publications

References 102 publications

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

Genome‐wide examination of myoblast cell cycle withdrawal during differentiation

IGF-1 activates the P13K/AKT signaling pathway via upregulation of secretory clusterin

IGF-binding protein-5: flexible player in the IGF system and effector on its own

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