COX2 EXPRESSION IN GENITOURINARY CANCER AND DEVELOPMENT

环氧合酶（考克斯）在细胞代谢中起着重要作用，介导花生四烯酸转化为具有生物活性的花生四烯酸。COX2是第二种促分裂原诱导型同种型，它的发现几乎与服用包括阿司匹林和其他非类固醇抗炎药（NSAID）在内的环氧合酶抑制剂的患者患克隆和其他癌症的风险降低近40%的认识同时发生。最近的研究证实，COX 2在包括结肠前列腺在内的特定上皮癌细胞亚群中异常增加，在包括结肠、前列腺、膀胱在内的特定上皮癌细胞亚群中异常增加。COX2抑制剂在各种实验模型中显著减缓这些肿瘤的生长。此外，观察到C0X2敲除小鼠和子宫内暴露于C0X2选择性NSAID的小鼠表现出严重的肾发育不全，表明C0X2在正常肾发育和泌尿生殖功能的发育和维持中具有特异性和关键性作用。COX 2在泌尿生殖道中的表达是任何正常组织中最高的。COX 2在泌尿生殖道中的表达是任何正常组织中最高的。COX 2在正常泌尿生殖道和上皮癌的生长和进展中的特殊重要性的因素是未知的。所提出的研究的目的是1）开发表达由COX2启动子驱动的GFP报告基因的小鼠，以促进从发育中的小鼠和患有泌尿生殖系统癌症的小鼠中分离活的COX2表达细胞。具体目标#2是从发育中的泌尿生殖道和鼠肿瘤组织开发细胞系，其将允许COX2阳性和OX2阴性细胞的遗传和功能区别。这些细胞的分离应该提供一种鉴定那些在癌症中引起COX 2异常上调的因子以及COX 2沿GU道沿着正常程序性表达的手段。这些细胞的分离将允许表征由COX2过表达细胞合成的前列腺素类概况，这将阐明COX2如何抑制膀胱前列腺和其他组织中的癌症进展。

Cyclooxygenase (COX) play a critical role in cellular metabolism, mediating the conversion of arachidonate to a family of bioactive prostaglandins. The discovery of COX2, a second, mitogen inducible isoform, occurred almost simultaneously with realization that patients taking cyclooxygenase inhibitors including aspirin and other non-steroid anti-inflammatory drug (NSAIDs) had nearly a 40% risk reduction of clon and other cancers. Recent studies confirm that COX2 is aberrantly increased in specific epithelium cancer cell sub-populations including colonic prostate, aberrantly increased in specific epithelial cancer cell sub-populations including colonic, prostate, bladder. COX2 inhibitors significantly slow growth of these tumors in a variety of experimental models. Additionally, the observation that COX2 knockout mice and mice exposed to COX2 selective NSAIDs in utero exhibit sever renal dysgenesis suggests a specific and critical role for COX2 in the development and maintenance of normal renal development and genitourinary function. Expression of COX2 in the genitourinary tract is among the highest of any normal tissue. Expression of COX2 in the genitourinary tract is among the highest of any normal tissue. The factors contributing to the particular importance of COX2 in the normal genitourinary tract and in the growth and progression of epithelial cancers are uncharacterized. The aim of the proposed studies is to 1) develop a mouse expressing a GFP reporter driven by the COX2 promoter to facilitate the isolation of viable COX2 expressing cells from developing mouse and mice with genitourinary cancers. Specific Aim #2 is to develop cell lines from the developing genitourinary tract and murine neoplastic tissue which will allow genetic and functional distinction of COX2 positive and OX2 negative cells. The is9olation of these cells should provide a means of identifying those factors responsible for aberrant up-regulation of COX2 in cancers, and normal programmed expression of COX2 along the GU tract. Isolation of these cells will allow characterization of the prostanoid profile synthesized by COX2 over- expressing cells which should clarify how COX2 inhibitors progression of cancer in the bladder prostate, and other tissues.