Effects Of UV And Gadd45 α On The Pathogenesis Of Cutaneous Squamous Cell Carcinoma

Gadd45a is one of Gadd (growth-arrest and DNA damage-inducible genes) gene family. It plays an important role in controlling cell cycle, repairing damaged DNA, inducing cell apoptosis and inhibiting tumor growth. Gadd45a is reduced in a number of cancer types and a bridge in the cascade process of apoptosis of tumor cells and maintaining genomic stability. Skin cancer is the most frequent form of malignancy in the world, and UV radiation is the primary environmental carcinogen responsible for its development. Gadd45a is a critical factor protecting the epidermis against UV radiation-induced tumorigenesis by promoting damaged keratinocytes to undergo apoptosis and/or cell cycle arrest. In this study, we are tentative to regulate the expression of Gadd45a on the HaCaT and A431 cells and investigate its effects on the proliferation and apoptosis of cells by using different methods.Part 1 Effects of Norrow-Band UVB on the expression of Gadd45a and proliferation,apoptosis in HaCaT cellsGadd45a mRNA and protein were improved after NB-UVB irradiation. Growth suppression was observed in a dose and time-dependent manner after NB-UVB irradiation. G2 phase arrest and enhanced cell apoptosis were also observed. NB-UVB showed effects on Gadd45a expression by which they may play roles in accommodating with proliferation suppression and cycle arrest process.Part 2 Expression difference of Gadd45a between HaCaT and A431 cellsRT-PCR, western blot and cell immunohistochemistry technique were applied to detect the expression of Gadd45a in cultured HaCaT and A431 cells. The results showed Gadd45a expression may keep the proliferation and differentiation of HaCaT cells; lower expression may be involved the malignant biological behaviors of A431 cells.Part3 Effects of Trichostatin A on the expression of Gadd45a and proliferation,apoptosis in A431 cellsCultured A431 cells were treated with different doses of Trichostatin A. Growth suppression was observed in a dose and time-dependent manner. Cell cycle was blocked at G1 phase and apoptosis ratio was increased. Gadd45a mRNA and protein expression of A431 cells were induced by Trichostatin A.Thus we proposed that Gadd45a may be involved in the course of cell proliferation suppression, cycle block, and apoptosis.Part 4 Gadd45a protein expression in cutaneous squamous cell carcinomaImmunohistochemical examination revealed that the positive expression rate of Gadd45a protein was significantly higher than normal skin which may play a role in the malignant process of cutaneous squamous cell carcinoma.Based on the results above, we drew the following conclusions:up-expression of Gadd45a in HaCaT and A431 cells may induce cell cycle block and apoptosis; the expression of Gadd45a may play a role in the pathogenesis of cutaneous squamous cell carcinoma.