Overexpression of Desmoglein 2 in a Mouse Model of Gorlin Syndrome Enhances Spontaneous Basal Cell Carcinoma Formation through STAT3-Mediated Gli1 Expression.

ABSTRACT: Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1^+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1^+/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1^+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated

SUBMITTER: Brennan-Crispi DM 

PROVIDER: S-EPMC6342634 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature