Premium
Aberrant expression and regulation of hepatic epidermal growth factor receptor in a c‐myc transgenic mouse model
Author(s) -
Woitach Joseph T.,
Conner Elizabeth A.,
Wirth Peter J.,
Thorgeirsson Snorri S.
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19970315)64:4<651::aid-jcb13>3.0.co;2-f
Subject(s) - epidermal growth factor , receptor , biology , tgf alpha , microbiology and biotechnology , hepatocyte , in vivo , transcription factor , hepatocyte nuclear factor 4 , endocrinology , nuclear receptor , in vitro , biochemistry , gene
In an attempt to elucidate the mechanism by which c‐myc and transforming growth factor‐α (TGF‐α) cooperate in hepatocyte tumor development, we have analyzed signaling by the epidermal growth factor (EGF) receptor and the consequent regulation of receptor number in transgenic mice bearing the c‐myc transgene under the control of the albumin enhancer/promoter. 125 I‐EGF binding and Scatchard analysis indicated a single class of high affinity receptors with the total number of binding sites of 1.2 × 10 4 ± 600 and 2.5 × 10 5 ± 1000 sites/cell in the normal and c‐myc hepatocytes in primary culture, respectively. After 72 h of EGF exposure in culture, the number of detectable EGF receptors on the cell surface of the c‐myc hepatocytes was not reduced, whereas the number of EGF receptors on normal hepatocytes was reduced to 32% that of untreated hepatocytes. Nuclear run‐on experiments done with nuclei isolated from intact livers demonstrated that transcription of the EGF receptor was 4.9‐fold higher in c‐myc mice. Increased levels of the transcriptional factor SP1 in the c‐myc hepatocytes in vivo and in primary culture, suggest a mechanism for the increased transcription of the EGF receptor. c‐myc also increases the expression of TGF‐α; a consequent increase in tyrosine phosphorylation is also detected in vivo. Thus, the increased number of EGF receptors in c‐myc expressing hepatocytes, even after prolonged exposure to EGF, or TGF‐α in vivo, may allow greater triggering of the EGF receptor signaling cascade. J. Cell. Biochem. 64:651–660. © 1997 Wiley‐Liss, Inc. This article is a U.S. Government work and, as such, is in the public domain in the United States of America.