Basic–Liver, Pancreas, and Biliary TractDiverse expression of ErbB receptor proteins during rat liver development and regeneration☆,☆☆
Section snippets
Animals
Male Sprague–Dawley rats (150–200 g) from Harlan (Indianapolis, IN) were housed under conditions of regulated lighting (lights on from 6 AM to 6 PM) and ad libitum access to water and Purina rodent chow (Ralston-Purina, St. Louis, MO). For the developmental study, timed pregnant female rats were obtained from Harlan and rat pups harvested surgically or postpartum. All protocols used were approved in advance by the Animal Use Subcommittee of the Vanderbilt Animal Care Committee.
Partial
ErbB receptor expression during liver development
To evaluate ErbB protein expression in hepatic development, ErbB proteins were immunoprecipitated from liver lysates (800 μg) and then immunoblotted with the immunoprecipitating antibodies. Immunoprecipitates were prepared from whole rat embryos at E16, embryonic rat liver at E19, neonatal liver (~24 hours after birth), and 1, 2, and 3 weeks postpartum liver using Western analysis. Bands corresponding to the 170- to 185-kilodalton forms of ErbB1, ErbB2, and ErbB3 were detected at various
Discussion
Examination of the expression levels of hepatic ErbB receptors in embryonic, neonatal weanling, and adult rats showed that EGF-R, ErbB2, and ErbB3 are differentially expressed during the development of rat liver (Figure 1). As suggested by the normal liver development in EGF-R/null25, 26 and kinase-impaired wa-2 mice,27 EGF-R signaling does not seem to be required for hepatic organogenesis. EGF binding and EGF-dependent kinase activity have previously been shown to be absent from the liver
Acknowledgements
The authors thank Dr. Arnold Strauss for support and encouragement, Silvio Sitaric for technical assistance, Dr. David Threadgill for critical review of this manuscript, and Dr. Snorri Thorgeirsson for providing us with the RLE cell line.
References (52)
- et al.
Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-alpha
Gastroenterology
(2001) - et al.
c-erbB-2 oncogene expression in hepatocellular carcinoma and cholangiocarcinoma
J Hepatol
(1992) - et al.
Insulin regulates heregulin binding and ErbB3 expression in rat hepatocytes
J Biol Chem
(1996) - et al.
Mitogen-independent DNA synthesis by fetal rat hepatocytes in primary culture
Exp Cell Res
(1993) - et al.
Mice with a null mutation of the TGF alpha gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation
Cell
(1993) Regulation of epidermal growth factor receptor levels by thyroid hormone
J Biol Chem
(1984)Biological clocks and the digestive system
Gastroenterology
(2000)- et al.
p120cbl is a cytosolic adapter protein that associates with phosphoinositide 3-kinase in response to epidermal growth factor in PC12 and other cells
J Biol Chem
(1996) - et al.
The coupling between transforming growth factor-alpha and the epidermal growth factor receptor during rat liver regeneration
Exp Cell Res
(1993) - et al.
Similar induction of the hepatic EGF receptor in vivo by EGF and partial hepatectomy
Biochem Biophys Res Commun
(1990)
Cell proliferation and oncogene expression after bile duct ligation in the rat: evidence of a specific growth effect on bile duct cells
Hepatology
Effect of epidermal growth factor (EGF) on [3H]TdR incorporation into DNA in ad lib fed and fasted CD2F1 mice
Peptides
Epidermal growth factor-induced phosphatidylinositol 3-kinase activation and DNA synthesis
Identification of Grb2-associated binder 2 as the major mediator in rat hepatocytes
J Biol Chem
Origin and structural evolution of the early proliferating oval cells in rat liver
Am J Pathol
Differential regulation of endogenous glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE-hepatoma cells
Biochem Biophys Res Commun
The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen
Nature
Specificity within the EGF family/ErbB receptor family signaling network
Bioessays
Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics
J Cell Biol
An essential role for ectodomain shedding in mammalian development
Science
HER2/neu: mechanisms of dimerization/oligomerization
Oncogene
ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling
EMBO J
ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner
Mol Cell Biol
The type 1 growth factor receptor family: new ligands and receptors and their role in breast cancer
Breast Cancer Res Treat
Hepatitis C virus genotyping in relation to neu-oncoprotein overexpression and the development of hepatocellular carcinoma
J Med Microbiol
Light and electron microscopical demonstration of c-erB-2 gene product-like immunoreactivity in human malignant tumors
Virchows Arch B Cell Pathol
Immunoreactivity for c-erbB-2 oncopeptide in benign and malignant diseases of the liver
Am J Clin Pathol
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2018, Biochimica et Biophysica Acta - Gene Regulatory MechanismsCitation Excerpt :Our analysis revealed upregulation of many ErbB-associated genes, including Erbb2. Of note, ERBB2 is strongly expressed in the embryonic liver and not in the adult liver [42], suggesting there may be a transcriptional switch that occurs during hepatic differentiation. Our observations contribute to growing evidence showing multiple levels of interaction between the Hippo pathway and growth factor-induced signaling pathways.
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Address requests for reprints to: William E. Russell, M.D., Division of Pediatric Endocrinology, T-0107 Medical Center North, Vanderbilt University, Nashville, Tennessee 37232-2579. e-mail: [email protected]; fax: (615) 343-5845.
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Supported by National Institutes of Health grant DK 53804 (to W.E.R.).