Activator Protein-1 Activity Regulates Epithelial Tumor Cell Identity

The study investigated the role of activator protein-1 (AP-1) in skin by using transgenic mice that conditionally express A-FOS, an inhibitor of AP-1. Older mice developed mild alopecia and sebaceous gland hyperplasia. During chemical-induced skin carcinogenesis, inhibiting AP-1 prevented typical squamous lesions and led to benign sebaceous adenomas with H-ras mutations. Inhibiting AP-1 in existing tumors caused squamous tumors to become sebaceous tumors, and reactivating AP-1 reversed this. Tumor cells expressed markers for both lineages, indicating multipotency. AP-1 was found to regulate the balance between wnt/β-catenin and hedgehog pathways, crucial for maintaining squamous tumor identity.