Role of VEGF in the growth and metastasis of a murine bladder carcinoma

Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum,and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not been clearly elucidated. Here, we dissected the effect of VEGF during bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell line BTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in-more than 80% reduction in VEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were minimal vascularization, extensive necrosis and longer latency compared to those formed by parental cells. The permeability of tumor vasrulatuce and metastatic tumor growth were also significantly suppressed in antisense VEGF cDNA transfected cells. In addition, the transfer of anti-angiogenic gene in a rumbination of sFlk-I and ExTek with electroporation can suppress the tumor growth efficiently. Taken together,these results demonstrated that VEGF plays an important role in bladder tumor angiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.     

基因狩猎：功能克隆定位克隆和表型克隆

致病基因的成功分离使人类能够深入洞察遗传性疾病的发病机理,并能对其进行科学的诊断和防治,同时也直接促进了生物高技术的进步,因此,它是现代遗传学最激动人心的领域.本文论述了基因克隆的发展历程和三种主要策略即功能克隆、定位克隆和表型克隆及其基本原理和重要成就,并展望了发展趋势.随着人类基因组计划的进展,定位克隆的一个新版本——定位候选基因技术正成为基因克隆的一种快捷高效的策略;表型克隆具有高度覆盖面和解析力,对复杂遗传病相关基因的围猎有独特的价值.