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Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin‐like growth factor‐1
Author(s) -
Vardy Daniel A.,
Kari Csaba,
Lazarus Gerald S.,
Jensen Pamela J.,
Zilberstein Asher,
Plowman Gregory D.,
Rodeck Ulrich
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041630206
Subject(s) - autocrine signalling , paracrine signalling , tgf alpha , epidermal growth factor , amphiregulin , growth factor , insulin like growth factor , biology , epidermal growth factor receptor , keratinocyte , growth factor receptor inhibitor , medicine , endocrinology , receptor , microbiology and biotechnology , cell culture , biochemistry , genetics
Autocrine activation of the epidermal growth factor (EGF) receptor on keratinocytes has been recognized as an important growth regulatory mechanism involved in epithelial homeostasis, and, possibly, hyperproliferative diseases. Insulin‐like growth factor (IGF)‐1 and insulin have been shown to be paracrine keratinocyte mitogens that bind to the type I IGF receptor which is expressed on actively proliferating keratinocytes in situ. In this report, we demonstrate that IGF‐1/insulin induced production of keratinocyte‐derived autocrine growth factors that bind to the EGF receptor. Increased steady‐state mRNA levels for transforming growth factor alpha (TGF‐α) and for amphiregulin (AR) were observed upon incubation of keratinocytes with mitogenic concentrations of IGF‐1. IGF‐1 also induced production and secretion of TGF‐α and AR proteins as detected by immunoassays. An EGF receptor antagonistic monoclonal antibody abolished the mitogenic effect of IGF‐1 on cultured keratinocytes. These results suggest that stimulation of keratinocyte growth by IGF‐1 requires activation of an EGF receptor‐mediated autocrine loop. © 1995 Wiley‐Liss, Inc.