Spontaneous Squamous Cell Carcinoma Induced by the Somatic Inactivation of <i>Retinoblastoma</i> and <i>Trp53</i> Tumor Suppressors

The study investigated the effects of simultaneously inactivating the Trp53 and retinoblastoma (Rb) genes in mouse epidermis using the Cre-loxP system. It was found that the loss of p53 alone led to spontaneous tumor development, highlighting p53 as the primary tumor suppressor in mouse epidermis. While the simultaneous inactivation of both pRb and p53 did not worsen the proliferation or differentiation phenotype seen in Rb-deficient epidermis, it significantly accelerated the development of aggressive and undifferentiated squamous cell carcinomas (SCC) originating from hair follicles. This acceleration was linked to the premature activation of the epidermal growth factor receptor/Akt pathway, which increased proliferation in normal and dysplastic hair follicles and enhanced tumor angiogenesis. The findings provided insights into epidermal tumor formation and could aid in developing therapies for aggressive squamous cancer.