An Estrogen Receptor/E2F1/CDKN3 Axis Protects from UV-induced Skin Cancers in Females

ABSTRACT: Men have a higher risk of developing cutaneous squamous cell carcinoma (SCC) compared with women, but models and comprehensive analyses of signaling pathways highlighting this sexual dimorphism are missing. Here, we use a UV-induced SCC model in hairless mice recapitulating this sex difference, with enhanced SCC development in males. While UV-induced DNA damage is similar between sexes, we uncover sex-specific responses in epidermal proliferation and differentiation. Global transcriptional profiling identifies E2F transcription factors as key sex-specific markers of the proliferative response to UV. E2F1/2 and their target gene CDKN3 are selectively downregulated in female mouse and human epidermis following UV exposure, and this is mediated by estrogen receptors. CDKN3 depletion impairs S

SUBMITTER: Celine Lukowicz 

PROVIDER: S-SCDT-10_1038-S44319-026-00743-2 | biostudies-other |

REPOSITORIES: biostudies-other