Human EGF Receptor (HER) Family and Heregulin Members Are Differentially Expressed in Epidermal Keratinocytes and Modulate Differentiation

Authors: De Potter I.Y.¹; Poumay Y.¹; Squillace K.A.²; Pittelkow M.R.²

Source: Experimental Cell Research, Volume 271, Number 2, December 2001 , pp. 315-328(14)

Publisher: Academic Press

Abstract:

Human EGF receptor (HER), also designated HER1, is an activatable tyrosine kinase receptor. HER1 activation regulates cell growth and differentiation in epidermal keratinocytes. Expression of other HER family members was investigated in human keratinocytes cultured under autocrine conditions. HER2 and HER3 are expressed and upregulated by confluence, concurrent with induction of epidermal differentiation. HER4 is not expressed by keratinocytes. Maximum expression of the cognate ligand, heregulin, is observed in subconfluent keratinocytes, and the expression of both heregulin and isoforms is downregulated with confluence. Recombinant heregulin isoforms have no effect on colony formation and keratinocyte proliferation, but heregulin activates tyrosine phosphorylation of HER2 and HER3, with no effect on HER1, in confluent differentiating keratinocyte cultures. Also, heregulin increases HER2/HER3 heterodimerization under those conditions. Treatment of confluent cultures by heregulin correlates with cell signaling and inhibition of epidermal differentiation. Together, HER2, HER3, and heregulin constitute a potential autocrine–paracrine system involved in epidermal homeostasis and repair, as well as in hyperproliferative pathologies. ©2001 Elsevier Science.

Keywords: keratinocyte; differentiation; heregulin; neuregulin; HER

Language: English

Document Type: Research article

Affiliations: 1: Département Histologie–Embryologie, Facultés Universitaires Notre-Dame de la Paix, 61 Rue de Bruxelles, Namur, B-5000, Belgium 2: Department of Dermatology, Mayo Clinic/Foundation, Rochester, Minnesota, 55905

Publication date: 2001-12-01

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