The combination of epidermal growth factor and glycogen synthase kinase 3 inhibitor support long-term self-renewal of Sca-1 positive hepatic progenitor cells from normal adult mice

Glycogen synthase kinase 3 (GSK3) was inhibited by 50% within 5 min when A431 cells were stimulated with epidermal growth factor (EGF). The inhibition was unaffected by rapamycin at concentrations which blocked the activation of p70 S6 kinase, and reversed by incubation with protein phosphatase-1. EGF stimulation of A431 cells inhibited GSK3 alpha and GSK3 beta to a similar extent, and inhibition was accompanied by phosphorylation of the tryptic peptides containing the serine residues phosphorylated in vitro by p70 S6 kinase or MAP kinase-activated protein (MAPKAP) kinase-1 beta (also termed Rsk-2). These results demonstrate that EGF inhibits GSK3 by inducing phosphorylation of a serine residue and that GSK3 is not phosphorylated in vivo by either p70 S6 kinase or protein kinase C.

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Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers

Journal of Neurosurgery ◽

10.3171/2017.2.jns153004 ◽

2018 ◽

Vol 129 (3) ◽

pp. 805-814 ◽

Cited By ~ 4

Author(s):

Eric D. Young ◽

Davis Ingram ◽

William Metcalf-Doetsch ◽

Dilshad Khan ◽

Ghadah Al Sannaa ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Peripheral Nerve ◽

Tumor Cells ◽

Tissue Microarray ◽

Growth Factor Receptor ◽

Nerve Sheath ◽

Epidermal Growth

OBJECTIVEWhile sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS.METHODSPatients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121).RESULTSSPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor–β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor–2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018).CONCLUSIONSComplete resection is curative for SPS. Left untreated, however, these tumors can cause significant morbidity, and not all patients are candidates for resection. SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2–associated schwannomas, suggesting a shared etiology. This SPS pattern is distinct from that of other tumors of the peripheral nerve sheath.

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Effects of epidermal growth factor and basic fibroblast growth factor on generation of long-term potentiation in the dentate gyrus of fimbria-fornix-lesioned rats

Brain Research ◽

10.1016/0006-8993(92)91332-9 ◽

1992 ◽

Vol 593 (2) ◽

pp. 335-338 ◽

Cited By ~ 46

Author(s):

Kazuho Abe ◽

Junichi Ishiyama ◽

Hiroshi Saito

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Dentate Gyrus ◽

Fibroblast Growth Factor ◽

Basic Fibroblast Growth Factor ◽

Long Term Potentiation ◽

Fibroblast Growth ◽

Term Potentiation ◽

Epidermal Growth

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Laminin γ3 Chain Binds to Nidogen and Is Located in Murine Basement Membranes

Journal of Biological Chemistry ◽

10.1074/jbc.m501875200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 22146-22153 ◽

Cited By ~ 45

Author(s):

Nikolaus Gersdorff ◽

Eddie Kohfeldt ◽

Takako Sasaki ◽

Rupert Timpl ◽

Nicolai Miosge

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Self Assembly ◽

Mammalian Cells ◽

Polyclonal Antibodies ◽

Basement Membranes ◽

Electron Microscopic ◽

Immunogold Staining ◽

Adult Mice ◽

Epidermal Growth

Recently a novel laminin γ3 chain was identified in mouse and human and shown to have the same modular structure as the laminin γ1 chain. We expressed two fragments of the γ3 chain in mammalian cells recombinantly. The first, domain VI/V, consisting of laminin N-terminal (domain VI) and four laminin-type epidermal growth factor-like (domain V) and laminin N-terminal modules, was shown to be essential for self-assembly of laminins. The other was domain III3–5, which consists of three laminin-type epidermal growth factor-like modules and is predicted to bind to nidogens. The γ3 VI/V fragment was a poor inhibitor for laminin-1 polymerization as was the β2 VI/V fragment. The γ3 III3–5 fragment bound to nidogen-1 and nidogen-2 with lower affinity than the γ1 III3–5 fragment. These data suggested that laminins containing the γ3 chain may assemble networks independent of other laminins. Polyclonal antibodies raised against γ3 VI/V and γ3 III3–5 showed no cross-reaction with homologous fragments from the γ1 and γ2 chains of laminin and allowed the establishment of γ chain-specific radioimmunoassays and light and electron microscopic immunostaining of tissues. This demonstrated a 20–100-fold lower content of the γ3 chain compared with the γ1 chain in various tissue extracts of adult mice. The expression of γ3 chain was highly tissue-specific. In contrast to earlier assumptions, the antibodies against the γ3 chain showed light microscopic staining exclusively in basement membrane zones of adult and embryonic tissues, such as the brain, kidney, skin, muscle, and testis. Ultrastructural immunogold staining localized the γ3 chain to basement membranes of these tissues.

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