INDUCTION OF AUTOCRINE EPIDERMAL GROWTH-FACTOR RECEPTOR LIGANDS IN HUMAN KERATINOCYTES BY INSULIN INSULIN-LIKE GROWTH-FACTOR-I

被引:38
作者
VARDY, DA
KARI, C
LAZARUS, GS
JENSEN, PJ
ZILBERSTEIN, A
PLOWMAN, GD
RODECK, U
机构
[1] WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104
[2] UNIV PENN,DEPT DERMATOL,PHILADELPHIA,PA 19104
[3] RHONE POULENC RORER,COLLEGEVILLE,PA 19426
[4] BRISTOL MYERS SQUIBB CO,SEATTLE,WA 98121
关键词
D O I
10.1002/jcp.1041630206
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 ICF-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-alpha) and for amphiregulin (AR) were observed upon incubation of keratinocytes with mitogenic concentrations of ICF-1. IGF-1 also induced production and secretion of TGF-alpha 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. (C) 1995 Wiley-Liss, Inc.
引用
收藏
页码:257 / 265
页数:9
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