Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1.

Published

Journal Article

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-alpha) 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-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 of IGF-1 requires activation of an EGF receptor-mediated autocrine loop.

Full Text

Duke Authors

Cited Authors

  • Vardy, DA; Kari, C; Lazarus, GS; Jensen, PJ; Zilberstein, A; Plowman, GD; Rodeck, U

Published Date

  • May 1995

Published In

Volume / Issue

  • 163 / 2

Start / End Page

  • 257 - 265

PubMed ID

  • 7706370

Pubmed Central ID

  • 7706370

Electronic International Standard Serial Number (EISSN)

  • 1097-4652

International Standard Serial Number (ISSN)

  • 0021-9541

Digital Object Identifier (DOI)

  • 10.1002/jcp.1041630206

Language

  • eng