Amphiregulin carboxy-terminal domain is required for autocrine keratinocyte growth.

ABSTRACT: The EGFR ligand amphiregulin (AREG) has been implicated as an important autocrine growth factor in several epithelial malignancies and in psoriasis, a hyperproliferative skin disorder. To characterize the mechanisms by which AREG regulates autocrine epithelial cell growth, we transduced human keratinocytes (KCs) with lentiviral constructs expressing tetracycline (TET)-inducible small hairpin RNA (shRNA). TET-induced expression of AREG shRNA markedly reduced autocrine extracellular signal-regulated kinase phosphorylation, strongly inhibited autocrine KC growth with an efficiency similar to metalloproteinase and EGFR inhibitors, and induced several markers of KC differentiation, including keratins 1 and 10. Addition of various concentrations of exogenous EGFR ligands to KC cultures reversed

SUBMITTER: Stoll SW 

PROVIDER: S-EPMC3072808 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature