| Skin cancer is one of the most susceptible cancer, and each year the incidence is over a million and there is a rising trend year by year. So it received attention. According to the degree of risk, skin cancer can be divided into three types, respectively:basal cell carcinoma, squamous cell carcinoma, and melanoma. Among them, the basal cell carcinoma and squamous cell carcinoma is the most common skin cancer. Squamous cell carcinoma (SCC) is derived from epithelial tissue of a malignant keratinocytes, develop fast, easy transfer, and easy to occur in the exposed parts, such as head, face, neck and back, is also found in oral mucosa, Lips, tongue, vulva and other parts.Gpr48is one of G protein-coupled receptors that has been found in recent years. Gpr48is widely expressed in human and mouse embryonic and adult tissues, suggesting that it may play an important role in the normal tissues and organs during development. It has proved that Gpr48has a lot of expression in the skin, improves that Gpr48may play a certain role in the skin to maintain normal metabolic activity. This article aims to explore the role of Gpr48in the squamous cell cancer and to find targets of drug treatment for the skin cancer. This research can be divided into two aspects:1Establishing a mouse model of squamous cell carcinoma, initially judged the role of Gpr48in the development of cutaneous squamous cell carcinoma.Squamous cell carcinoma is induced by DMBA/TPA two-steps method. We choose Gpr48+/+group, Gpr48+/-group, and Gpr48-/-group mice as experimental objects. We found that, Gpr48deletion significantly reduced tumor multiplicity (P<0.01), tumor incidence was significantly lower (P<0.05) and tumor size was significant reduction (P<0.001). Gpr48deletion can significantly inhibit cutaneous squamous cell carcinoma development induced by DMBA/TPA.2Found the molecular mechanism that lack of Gpr48inhibits the development of cutaneous squamous cell carcinomaBy immunohistochemistry and HE staining, we found that Gpr48deletion decreased PCNA expression in the epidermal tissue, and also significantly inhibited the hyperplasia of skin conditions. Using Real time Quantitative PCR method to detect that, Gpr48deficiency can significantly reduce PKCa (P<0.05), PKC y (P <0.01) and PKC5(P<0.01) on the transcriptional level, Also significantly reduced the c-jun (P<0.05) and c-fos (P<0.05) on the transcriptional level. Inflammatory cytokines CD31and IL-6were also detected. After Gpr48deletion, CD31and IL-6levels were significantly increased (P<0.01, P<0.05). Cultured squamous cell carcinoma cell line A431, using ShRNA interference Gpr48gene expression. Gpr48knockout efficiency is70%. After TPA stimulation, the expression of PKC5was significantly lower (P<0.05), And c-jun and c-fos phosphorylation was significantly lower (P<0.05, P<0.05) in the Gpr48knockout cells.Consequently, we can conclude as follows:1Using DMBA/TPA induced skin cancer formation, was an effective way to study squamous cell cancer mechanisms and treatment.2Gpr48gene deletion decreased tumor multiplicity, tumor incidence and tumor size significantly. Gpr48deletion can effectively inhibit the TPA-induced skin squamous cell carcinoma development.3Gpr48deletion can significantly reduce PCNA expression in the mouse epidermis, and also significantly inhibite the hyperplasia skin conditions. TPA can stimulate the expression of PKC, and Gpr48deletion can significantly reduce the expression level of PKC, thereby reducing AP-1(c-jun and c-fos) expression. |
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