Document Detail


Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo.
MedLine Citation:
PMID:  12435727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epidermal growth factor receptor (EGFR) overexpression is observed in a number of malignancies, especially those of esophageal squamous cell origin. However, little is known about the biological functions of EGFR in primary esophageal squamous epithelial cells. Using newly established primary human esophageal squamous epithelial cells as a platform, we overexpressed EGFR through retroviral transduction and established novel three-dimensional organotypic cultures. Additionally, EGFR was targeted in a cell type- and tissue-specific fashion to the esophageal epithelium in transgenic mice. EGFR overexpression in primary esophageal keratinocytes resulted in the biochemical activation of Akt and STAT pathways and induced enhanced cell migration and cell aggregation. When established in organotypic culture, EGFR-overexpressing cells had evidence of epithelial cell hyperproliferation and hyperplasia. These effects were also observed in EGFR-overexpressing transgenic mice and the esophageal cell lines established thereof. In particular, EGFR-induced effects upon aggregation appear to be mediated through the relocalization of p120 from the cytoplasm to the membrane and increased interaction with E-cadherin. EGFR modulates cell migration through the up-regulation of matrix metalloproteinase 1. Taken together, the functional effects of EGFR overexpression help to explain its role in the initiating steps of esophageal squamous carcinogenesis.
Authors:
Claudia D Andl; Takaaki Mizushima; Hiroshi Nakagawa; Kenji Oyama; Hideki Harada; Katerina Chruma; Meenhard Herlyn; Anil K Rustgi
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2002-11-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-01-13     Completed Date:  2003-02-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1824-30     Citation Subset:  IM    
Affiliation:
Gastroenterology Division, Abramson Cancer Center and Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cell Aggregation / physiology*
Cell Division / physiology*
Cell Line
Cell Membrane / metabolism
Cell Movement / physiology*
Cytoplasm / metabolism
DNA Primers
Esophagus / cytology*
Humans
Keratinocytes / cytology
Mice
Mice, Transgenic
Protein Transport
Receptor, Epidermal Growth Factor / physiology*
Retroviridae / genetics
Transduction, Genetic
Grant Support
ID/Acronym/Agency:
CA 25874/CA/NCI NIH HHS; CA 80999/CA/NCI NIH HHS; P01 CA098101/CA/NCI NIH HHS; P01 DE12467/DE/NIDCR NIH HHS; P30 DK50306/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; EC 2.7.10.1/Receptor, Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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