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

Publication ,  Journal Article
Vardy, DA; Kari, C; Lazarus, GS; Jensen, PJ; Zilberstein, A; Plowman, GD; Rodeck, U
Published in: J Cell Physiol
May 1995

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.

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Published In

J Cell Physiol

DOI

ISSN

0021-9541

Publication Date

May 1995

Volume

163

Issue

2

Start / End Page

257 / 265

Location

United States

Related Subject Headings

  • Transforming Growth Factor alpha
  • Ligands
  • Keratinocytes
  • Intercellular Signaling Peptides and Proteins
  • Insulin-Like Growth Factor I
  • Insulin
  • Humans
  • Growth Substances
  • Glycoproteins
  • ErbB Receptors
 

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Vardy, D. A., Kari, C., Lazarus, G. S., Jensen, P. J., Zilberstein, A., Plowman, G. D., & Rodeck, U. (1995). Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1. J Cell Physiol, 163(2), 257–265. https://doi.org/10.1002/jcp.1041630206
Vardy, D. A., C. Kari, G. S. Lazarus, P. J. Jensen, A. Zilberstein, G. D. Plowman, and U. Rodeck. “Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1.J Cell Physiol 163, no. 2 (May 1995): 257–65. https://doi.org/10.1002/jcp.1041630206.
Vardy DA, Kari C, Lazarus GS, Jensen PJ, Zilberstein A, Plowman GD, et al. Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1. J Cell Physiol. 1995 May;163(2):257–65.
Vardy, D. A., et al. “Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1.J Cell Physiol, vol. 163, no. 2, May 1995, pp. 257–65. Pubmed, doi:10.1002/jcp.1041630206.
Vardy DA, Kari C, Lazarus GS, Jensen PJ, Zilberstein A, Plowman GD, Rodeck U. Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1. J Cell Physiol. 1995 May;163(2):257–265.
Journal cover image

Published In

J Cell Physiol

DOI

ISSN

0021-9541

Publication Date

May 1995

Volume

163

Issue

2

Start / End Page

257 / 265

Location

United States

Related Subject Headings

  • Transforming Growth Factor alpha
  • Ligands
  • Keratinocytes
  • Intercellular Signaling Peptides and Proteins
  • Insulin-Like Growth Factor I
  • Insulin
  • Humans
  • Growth Substances
  • Glycoproteins
  • ErbB Receptors