Epidermal overexpression of LRIG1 disturbs development and homeostasis in skin by disrupting the ERBB system

The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis

“…3). As observed for skin homeostasis [13], EGFR is significantly less phosphorylated during tumorigenesis (Fig. 3A,B).…”

“…While differentiation of the IFE of LRIG1‐TG mice was not affected, epidermal thickness was increased and the proliferation was significantly decreased. Under homeostatic conditions, LRIG1‐TG mice show also thickened epidermis but increased proliferation rate [13]. Consequently, the DMBA/TPA treatment may cause a less pronounced increase in epidermal thickness, which is in line with the decreased proliferation rate.…”

“…The mice had access to water and standard rodent diet (V1534; Ssniff, Soest, Germany) ad libitum . Mice overexpressing LRIG1 skin specifically under the control of the keratin 5 (KRT5) promoter using the tetracycline‐controlled transcriptional activation system (TET‐Off) have been originally described previously [13]. After positive copulatory plug check, pregnant mice received 3 mg·mL −1 doxycycline (Dox) [Beladox 500 mg·g −1 , bela‐pharm (Lehnecke 793‐588), Schortens, Germany] in the drinking water together with 5% sucrose (Sigma, Taufkirchen, Germany) until they gave birth to inhibit transgene expression during embryogenesis.…”

“…Lrig1 knockout mice show a severe epidermal, psoriasis‐like phenotype [18]. In previous studies, we have shown that the skin‐specific overexpression of LRIG1 affects skin morphogenesis as well as homeostasis by regulating ERBB signaling [13]. Moreover, LRIG1 upregulation in consequence of the skin‐specific overexpression of the EGFR ligand epigen during homeostasis [19], or owing to increased intrinsic EGFR signaling in epidermal papillomas of Egfr Dsk5 mice [9], indicates a function of LRIG1 in feedback regulation of the ERBB network also in the skin.…”

“…LRIG1 is one of three members of a transmembrane protein family (LRIG1-3) [12] and a negative regulator of ERBB receptors [13,14]. Additionally, LRIG1 promotes stem cell quiescence in the intestine [15], the stomach [16], and also in the skin [17].…”