Targeted Disruption of Bcl-xL in Mouse Keratinocytes Inhibits Both UVB- and Chemically Induced Skin Carcinogenesis

The study investigated the role of the antiapoptotic protein Bcl‐xL in skin carcinogenesis using Bcl‐xL-deficient mice. It was found that disrupting Bcl‐xL expression in mouse keratinocytes led to increased apoptosis in response to UVB irradiation and chemical treatment, specifically in the epidermis and hair follicle keratinocytes. Despite this increase in apoptosis, cell proliferation was unaffected. Bcl‐xL-deficient mice showed greater resistance to skin tumor development, with delayed onset and fewer tumors compared to wild-type controls. Additionally, levels of other antiapoptotic proteins like Bcl‐2, Mcl‐1, and survivin were elevated in the epidermis of Bcl‐xL-deficient mice. The findings suggested that Bcl‐xL contributed to early skin carcinogenesis by enhancing keratinocyte survival after DNA damage.