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- W3205734981 abstract "3886 The hedgehog (Hh) pathway plays a critical role in embryonic development and tissue polarity. Activation of Hh signaling, usually due to loss-of-function somatic mutations of PTCH1 and less often to activating mutations of SMO, is the pivotal abnormality in sporadic basal cell carcinomas (BCCs). A natural product, cyclopamine, can specifically inhibit Hh signaling and is shown to be effective in prevention and treatment of BCCs in animal models. There are several mouse models for Hh signaling-mediated BCC formation, with Ptch1+/- mice as one of the best models. However, about 30% of Ptch1+/- mice die from medulloblastoma and a long-term UV irradiation is required for BCC formation in this model, which prevents widely use of this mouse model for drug testing. To establish more efficient mouse models, we have generated mice with skin-specific activation of Hh signaling using K14 promoter. In this model, activation of hedgehog signaling was achieved by either skin-specific knockout of Ptch1 or skin-specific knockin of activated SMO. We found that these mice develop skin cancers in the first week. By day 28, most mice develop alopecia. These mice only have one third of the weight of the wild type mice. Skin of these mice is filled with BCC-like tumors. Further analysis of these tumors indicated that Hh signaling is activated. In summary, we have established novel mouse models for Hh signaling-mediated skin cancers. These mice can be readily used for testing therapeutic drugs for BCCs." @default.
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- W3205734981 date "2007-05-01" @default.
- W3205734981 modified "2023-09-28" @default.
- W3205734981 title "A novel mouse model for hedgehog signaling-mediated carcinogenesis" @default.
- W3205734981 hasPublicationYear "2007" @default.
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