The Epidermal Growth Factor Receptor; Studies in Cultured Hepatocytes and During Liver Regeneration

Earp, H. Shelton; Blaisdell, Joyce; Rubin, Richard A.; Lin, Qixiong

doi:10.1007/978-3-642-70956-2_25

Cited by 2 publications

(2 citation statements)

References 18 publications

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“…Activation of EGFR by EGF or TGFa upregulates the transcription of the TGFa gene (Coey et al, 1987;Bjorge et al, 1989) and its cognate receptor EGFR (Clark et al, 1985;Kudlow et al, 1986;Earp et al, 1986). Because of the evidence for crosstalk among the ErbB family of RTKs (for review, see Carraway and Cantley, 1994;Dougall et al, 1994), we examined whether the increased ErbB2 signaling caused an upregulation of endogenous TGFa and EGFR in the transgenic skin.…”

Section: Up-regulation Of Tgfa and Egfr Mrna Expression In Erbb2-overmentioning

confidence: 99%

Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFα expression in transgenic mice

et al. 1999

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The ErbB2 receptor tyrosine kinase (RTK) is expressed in basal cells of squamous epithelia and the outer root sheath of hair follicles. We previously showed that constitutive expression of activated ErbB2 directed to these sites in the skin by the keratin 14 (K14) promoter produces prominent hair follicle abnormalities and striking skin hyperplasia in transgenic mice. However, perinatal lethality precluded the establishment of a transgenic line for analysis of ErbB2 function in adult animals. To investigate the signi®cance of ErbB2 signaling in epithelial tissues during and post development, we developed a K14-rtTA/TetRE-ErbB2`Tet-On' bitransgenic mouse system. These mice were normal until the ErbB2 transgene was induced by exposure to doxycycline (Dox). Prenatal induction resulted in perinatal death. Postnatally, ErbB2 transgene expression was observed at 4 h after the initiation of Dox, and reached a plateau at 24 h. Skin hyperplasia followed after 2 days and these changes reverted to normal upon Dox withdrawal. In adults, as in the neonates, prolonged ErbB2 induction caused prominent skin and hair follicle hyperplasias. Severe hyperplasias in the cornea, eye lids, tongue and esophagus were also observed. ErbB2 transgene induction was accompanied by increased expression of TGFa, a ligand of epidermal growth factor receptor (EGFR), and to a lesser extent, EGFR, further enhancing RTK signal transduction. We conclude that ErbB2 plays important roles in both development and maintenance of hair follicles and diverse squamous epithelia and that this ligand-inducible and tissue-speci®c Tet-On' transgenic mouse system provides a means to study transgenes with perinatal toxicity.

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Section: Up-regulation Of Tgfa and Egfr Mrna Expression In Erbb2-overmentioning

confidence: 99%

Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFα expression in transgenic mice

et al. 1999

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“…In the absence of staurosporine, TPA stimulated the accumulation of both the EGF receptor and TGF-t~ mRNAs, while in its presence, this effect of TPA was completely blocked. EGF is also capable of stimulating EGF receptor [24,25] and TGF-~ mRNA [26[ accumulation in certain cells including the MDA468 cells. Staurosporine also blocked these EGF-stimulated effects.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of stimulus‐dependent epidermal growth factor receptor and transforming growth factor‐α mRNA accumulation by the protein kinase C inhibitor staurosporine

et al. 1989

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The ability of staurosporine, a potent inhibitor of protein kinase C, to block certain cellular events initiated by 12-0-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) was examined. Treatment of MDA468 breast cancer cells with TPA decreases EGF binding to the cell surface and this effect is blocked by pretreatment with staurosporine with an ICs0 of 30 nM. Either 10 -9 M EGF or 100 ng/ml TPA stimulated the accumulation of both EGF receptor and TGF-a mRNA and staurosporine (50 nM) completely abolished these mRNA accumulations. Staurosporine did not block EGF-stimulated tyrosine phosphorylation of its receptor as measured by immunoblotting with anti-phosphotyrosine antibodies. The ability of staurosporine to block the mRNA responses of either EGF or TPA suggests that these two agents have common signaling pathways and it implies a role for protein kinase C in the control of EGF receptor and TGF-~t expression.

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The Epidermal Growth Factor Receptor; Studies in Cultured Hepatocytes and During Liver Regeneration

Cited by 2 publications

References 18 publications

Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFα expression in transgenic mice

Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFα expression in transgenic mice

Inhibition of stimulus‐dependent epidermal growth factor receptor and transforming growth factor‐α mRNA accumulation by the protein kinase C inhibitor staurosporine

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