Liver epithelial cell migration induced by epidermal growth factor or transforming growth factor alpha is associated with changes in the gene expression of secreted proteins |
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Authors: | E G Bade S Feindler |
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Institution: | 1. Fakult?t für Biologie, Universit?t Konstanz, Postfach 5560, D-7750, Konstanz, Federal Republic of Germany
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Abstract: | Summary Rat liver epithelial cells are induced to migrate by epidermal growth factor (EGF) or transforming growth factor alpha (TGF-α)
in serum-free medium supplemented with insulin. Immunohistological staining of the migration tracks containing laminin and
fibronectin has allowed a quantitative analysis of the process. The growth factor-induced migration is relatively slow, but
very efficient. Between 24 and 48 h after exposure to EGF (or TGF-α), 50 to 70% of the cells have migrated away from their
site of initial attachment and spreading. This delayed effect of the interaction of the receptor with its ligands is associated
with changes in gene expression, but is not associated with a stimulation of cell proliferation. In serum-free medium supplemented
with insulin, the cells secrete six major proteins, as revealed by SDS-polyacrylamide gel electrophoresis. The media of cultures
supplemented with insulin plus EGF (or TGF-α) contain in addition two new proteins and an increased amount of fibronectin.
One secreted protein is synthesized in significantly reduced amounts. The most conspicuously EGF-induced protein (EIP-1, Mr
47 000) is detected within 2 h, depends on the continued presence of the growth factor, and has not been detected as bound
to the substratum. The stringent regulation of EIP-1 suggests that this gene product might participate in the modulation of
the changes induced by the growth factor. The system is being used for the further analysis of the regulation of gene expression
by EGF and of the migration of normal and neoplastically transformed epithelial cells.
This paper is dedicated to the memory of Dr. Luis F. Leloir.
A preliminary communication has been presented at the Cold Spring Harbor Meeting on Liver Gene Expression, May 1987.
Editor's Statement Mitogen-stimulated gnees are an active area of study with fibroblastic systems. In this paper the approach
is extended to epithelial cells and functional correlations are also made. |
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Keywords: | epidermal growth factor transforming growth factor alpha extracellular matrix migration tracks fibronectin gene expression |
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