DMBA/TPA Treatment Is Necessary for Basal Cell Carcinoma Formation from Patched Deficient Epidermal Cells in Ptch Flox/Flox CD4Cre +/- Mice

The document from 2014 presents a study on the development of basal cell carcinoma (BCC) in Ptchflox/flox CD4Cre+/- mice, which have a mutation in the Hedgehog (Hh) signaling pathway component Patched1 (Ptch). The study concluded that the formation of BCC in these mice requires both a genetic predisposition (biallelic loss of Ptch in CD4+ epidermal cells) and an environmental trigger (treatment with the carcinogens DMBA/TPA). The BCCs originated from Ptch-deficient epidermal cells, not from T cells or bone marrow-derived cells, and expressed Gli1, a marker of Hh pathway activation. The study also identified a nonhematopoietic CD4+ cell population in the skin that may be involved in BCC formation. The findings suggest that a second, unknown event, in addition to Ptch loss, is necessary for BCC development, and that the Ras signaling cascade is not implicated in this process.