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 mice with a targeted disruption of Bcl-xL in keratinocytes. It was found that Bcl-xL-deficient mice exhibited increased apoptosis in the epidermis and hair follicle keratinocytes, particularly in the bulge region, when exposed to UVB irradiation or DMBA treatment. Despite this increase in apoptosis, cell proliferation was unaffected. These Bcl-xL-deficient mice showed greater resistance to skin tumor development, with a delayed onset and reduced number of tumors compared to wild-type controls. Additionally, in the absence of stimuli, levels of other antiapoptotic proteins such as 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 the survival of keratinocytes, including stem cells in the bulge region, following DNA damage.