RasGRP1 transgenic mice develop cutaneous squamous cell carcinomas in response to skin wounding: Potential role of granulocyte colony-stimulating factor

摘要: Models of epidermal carcinogenesis have demonstrated that Ras is a critical molecule involved in tumor initiation and progression. Previously, we shown RasGRP1 increases the susceptibility mice to skin tumorigenesis when overexpressed epidermis by transgenic approach, related its ability activate Ras. Moreover, develop spontaneous papillomas cutaneous squamous cell carcinomas, some which appear originate sites injury, suggesting may be responding signals generated during wound-healing process. In this study, examined response animals full-thickness incision wounding skin, they respond developing tumors along wounded site. The did not present mutations H-ras gene, but Rasgrp1 transgene dosage correlated with size. Analysis serum cytokines showed increased levels granulocyte colony-stimulating factor after wounding. Furthermore, vitro experiments primary keratinocytes stimulated activation, although was dispensable for effect. Since has been recently associated proliferation cancer cells, our results help elucidation pathways absence oncogenic ras mutations.