SELECTED MECHANISMS OF HUMAN BLADDER CARCINOGENESIS

本项目的主题是研究选定的细胞 和生化事件，可能有助于恶性 正常人尿路上皮转化为尿路上皮癌。的 我们将研究的过程-染色体/遗传损失在多步骤 体外转化、靶组织的致癌活性和靶向 细胞对普遍存在的生长因子的反应性-都有很强的 有证据表明它们与尿路上皮细胞中的基本事件有关， 肿瘤发生 总体目标： 为了阐明正常的细胞成分和事件是如何被改变的 和/或“利用”其独特的环境，以促进 转化表型的表达。 具体目标：检验以下假设： * 染色体/遗传损失与肿瘤转化相关， 人尿路上皮细胞的体外和肿瘤进展。 * N-乙酰化酶和脱乙酰化酶在易感性中起决定性作用。 膀胱癌 * 芳胺膀胱致癌物的酶促活化和/或失活 由人类尿路感染发生，并影响个人的易感性， 患上膀胱癌的风险 * 后配体结合事件的改变发生在转化的细胞中。 移行上皮细胞，使他们，但不是他们的正常 一个人，被一个人所吸引，他们两个人， 持续暴露-表皮生长因子。 这些调查将提供深入了解肿瘤的过程， 发展和增长，并可能产生重要的信息， 临床分型、早期发现、预后、预防和 尿路上皮癌的治疗。

The theme of this program project is the investigation of selected cellular and biochemical events which may be instrumental in the malignant transformation of normal human urothelium into urothelial carcinoma. The processes we shall study- chromosomal/genetic loses in multistep transformation in vitro, carcinogen activity by target tissue, and target cell responsiveness to an ubiquitous growth factor - all have strong evidence linking them to fundamental events in urothelial cell tumorigenesis. Overall Objective: To elucidate how normal cellular components and events become altered and/or "take advantage" of their unique environment, to contribute to the expression of the transformed phenotype. Specific Aims: To test the following hypotheses: *Chromosomal/genetic losses correlate with tumorigenic transformation in vitro and neoplastic progression of human uroepithelial cells. *N-acetylases and deacetylases play a determinate role in susceptibility to bladder cancer. *Enzymatic activation and/or inactivation of arylamine bladder carcinogens by human urothelium occurs, and influences an individual's susceptibility for developing bladder cancer. *Alterations in post-ligand binding events occur in transformed transitional epithelial cells which enable them, but not their normal counterparts, to be stimulated by a mitogen to which they are both continually exposed - epidermal growth factor. These investigations will provide insights into the processes of neoplastic development and growth, and may yield information of importance for clinical classification, early detection, prognosis, prevention and treatment of urothelial cancers.