Data from Synergistic Function of Smad4 and PTEN in Suppressing Forestomach Squamous Cell Carcinoma in the Mouse

The study investigates the genetic basis of esophageal tumorigenesis by examining the effects of deleting the Smad4 and PTEN genes in mice. The simultaneous inactivation of these genes led to accelerated hair loss, skin tumor formation, and spontaneous forestomach carcinogenesis with complete penetrance within the first 2 months of age. All forestomach tumors were invasive squamous cell carcinomas, mimicking human esophageal SCCs, with some lesions also showing adenocarcinomas in adjacent submucosa. The rapid tumor progression was linked to increased epithelial proliferation and decreased expression of cell cycle inhibitors (p27, p21, p16) alongside overexpression of cyclin D1. The findings highlight the synergistic role of Smad4 and PTEN in suppressing forestomach tumorigenesis through the induction of cell cycle inhibitors.