动物造模 z-bio 2024-01-29 634

　　There are many reports on transgenic animal models related to tumor angiogenesis. There are currently three types of transgenic mouse models used for tumor angiogenesis:

　　1. The RIP-Tag transgenic mouse model is induced by the oncogene SV40Tag, controlled by the insulin gene regulatory region, and is composed of pancreatic islets β Cellular tumors. Oncogene expression can be observed at 8-21 days of embryonic stage, followed by scattered proliferation of islets, of which 50% become highly proliferative islets, possessing the characteristics of tumor cells in histological morphology and proliferation rate. Among them, 20% have obvious angiogenesis, and 10% can become solid tumors. Histological examination of newly formed blood vessels confirms that: ① The pre cancerous lesions in the RIP Tag transgenic mouse model are very obvious in all stages, with a angiogenesis phase after the proliferative phase. ② New blood vessels grow well before the tumor cells undergo extensive malignant transformation.

　　The BPV1.69 transgenic mouse model was induced by the human papillomavirus genome and is a skin fibrosarcoma. The tumor formation in this model can be divided into three stages: normal, mild skin fibroma formation, and invasive skin fibroma formation. The three stages are accompanied by the expression of c-jun, jun-B oncogenes, and their related transcription factors AP-1. Immunostaining with vWF (Von Willebrand) confirmed a significant increase in microvascular density during the formation stage of invasive skin fibroma. The results indicate that there is activation of blood vessels prior to the formation of skin fibrosarcoma. The experiments on in vitro cell lines also showed that at each stage of the gradual formation of skin fibrosarcoma, there were corresponding independent vascular initiation stages. The conditioned culture medium of normal skin cells and mild skin fibrosarcoma cells did not have the activity of promoting endothelial cell division and proliferation, while the conditioned culture medium of infiltrating skin fibrosarcoma cells and skin fibrosarcoma cells had the activity of promoting endothelial cell division and proliferation.

　　The K14-HPV16 transgenic mouse model is derived from basal keratinocytes and mainly expresses the human papillomavirus type 16 oncogene. It is controlled by the keratin 14 gene regulatory region and is a squamous cell carcinoma of the epidermis. This model exhibits activation of angiogenesis initiation at all stages of tumor formation. One month old K14-HPV16 transgenic mice showed a slight increase in the density of capillaries in the dermis, while in the early and advanced stages of dysplasia, a significant increase in both the number and distribution density of capillaries was observed. This phenomenon indicates that the formation of low-grade damaged blood vessels begins in the early stages, moving from a stationary state to a moderate degree of neovascularization, while the formation of blood vessels increases significantly in the highly proliferative and tumor infiltrating stages.