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

    March 2014 in “ Journal of Investigative Dermatology ”
    Anja Uhmann, Ina Heß, Anke Frommhold, Simone König, Sebastian Zabel, Frauke Nitzki, Kai Dittmann, Fred Lühder, Hans Christiansen, Julia Reifenberger, Walter Schulz–Schaeffer, Heidi Hahn
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    TLDR Genetic mutation and carcinogen treatment are both needed for skin cancer to develop in these specific 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.
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