The Pulmonary Tumorigenesis Induced by Human VEGF-A165 Overexpression in the Lung Tissue of Transgenic Mice

• Main Authors: Pin-Wu Huang, 黃彬武
• Other Authors: 陳全木
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/85930279443958198533

碩士 === 國立中興大學 === 生命科學系所 === 94 === Abstract The vascular endothelial growth factor (VEGF) family members consist of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor (PlGF). VEGF-A has at least nine subtypes due to the alternative splicing of a single gene and the the VEGF-A165 isoform plays a central role in vascular development. VEGF-A exhibits two major biological activities: One is the capacity to stimulate vascular endothelial cell proliferation, and the other is the ability to increase vascular permeability. VEGF-A also promotes the survival and migration of endothelial cells. VEGF-A and its receptor are involved in carcinogenesis, invasion and distant metastasis as well as tumor angiogenesis. Clara cell secretory protein (CCSP) is a protein that is secreted by nonciliated, nonmucous clara cells in the pulmonary airway. CCSP plays a protective role against pulmonary inflammatory response. CCSP is a potent natural immunosuppressor and anti-inflammatory agent. In this study, ccsp-Vegf-A165- sv40 poly(A) was constructed for the production of lung-specific overexpressing VEGF-A165 transgenic mice by microinjection. The results of PCR and Southern blot showed that there were three transgenic mice producted by that microinjection. Further, the results of Southern blot indicated there were the same patterns of the foreign gene within the genome of the transgenic founder mice and their offsprings. The data showed that Vegf-A165 mRNA can be expressed specifically in the lung tissue of the transgenic mice. And the results of Western blot also showed that the VEGF-A165 can be expressed in the lung tissue of the transgenic mice. In the histopathologic slides of the lung tissue in the transgenic mice, it seemed that VEGF-A165 overexpression can induce bronchial epithelium flattened(96%), abnormal proliferation of cells on bronchial epithelium(93%), inflammation(43%), fibrosis(40%), adenoma(18%) and cyst(18%) in the total examination of 32 transgenic mice. Further, the results showed that VEGF-A165 can promote phosphorylation of ERK2, increase the expression of cyclin D1 and survivin mRNA. All of the above suggest that VEGF-A165 induced the proliferation of cells on the bronchial epithelium of the transgenic mice through ERK1/2 MAPK pathway.