[Modeling mechanism] Transgenic animal models of bladder cancer can be divided into microinjection, retroviral infection and embryonic stem cell method through gene transfer. The microinjection method is more mature. The purified target gene fragments were microinjected into the fertilized egg, and then the target gene was randomly integrated into the mouse chromosomes and distributed to each cell as the embryo differentiated.
[Modeling method]
1. Studies on transgenic technology have shown that the 3.6 kb sequence upstream of the mouse Uroplakin II gene can lead to the expression of specific oncogenes in the urinary tract epithelium. The UPII-SV40T chimeric gene was constructed by fusing the sequence with the inducible oncoprotein gene SV40T. Transfected cell carcinomas produced by transfected mice are very similar to humans in phenotype and transformation pattern. Uroplakin II gene is used to promote the high expression of epidermal growth factor in the transitional epithelium of the urethra, and transgenic mice with high levels of epidermal growth factor receptor mRNA show obvious transitional epithelial proliferation and proliferating cell nuclear antigen. Found to have high expression. In addition, it was found that the combination of epidermal growth factor and SV40T transgenic mice can develop SV40T-induced epithelial cancer into high-grade bladder tumors. It can be seen that epidermal growth factor has a synergistic carcinogenic effect on SV40T.
2. Gene transfection studies have found that the transfection of H-ras and other oncogenes can lead to bladder transitional cell cancer. Bladder tumors with high expression of Cadherin S100A4 have a high incidence of bladder tumors and are easy to metastasize. The tumor is easily found in the orthotopic model of MY-3L tumor, which has growth and invasion, but no tumor metastasis. After transfecting the cells with a gene that induces high S100A4 expression, it was found to be significantly metastasized to the para-aortic lymph nodes and lungs, indicating that S100A4 gene transfection can optimize the bladder tumor metastasis model. There is a synergy between transfection and drug delivery. For example, mice transfected with the precancerous gene C-Ha-ras are more sensitive to bladder tumors induced by BBN.
[Model Evaluation and Application] Animal models of bladder cancer are gradually maturing, and their application scope is expanding to drug discovery. Currently, tumor cell transplantation bladder cancer models and animal models of bladder cancer induced by chemical carcinogens are still used more frequently. With the development of molecular biotechnology, gene transfer, microinjection of target gene fragments into fertilized eggs, and the use of embryo differentiation in somatic cells to form animal models of bladder cancer have been related to the etiology and biology of bladder cancer. Study science. Important behaviors and treatment methods can more objectively reflect the therapeutic effects of treatment factors on bladder cancer, and provide experimental evidence for the clinical application of various bladder cancer treatment methods.