MECHANISMS OF IMMUNE CLEARANCE FOR HPV POSITIVE CELLS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这个项目的总体目标是确定与头颈部恶性肿瘤的易感性和进展相关的遗传因素。目前的证据表明，头颈部癌症的发生与接触环境致癌物质(如吸烟和饮酒)和感染人类乳头瘤病毒(HPV)有关。HPV感染在一种称为口咽癌的头颈部癌症中占主导地位。例如，约50%的扁桃体癌含有和表达HPV序列。现在也有重要的证据表明，PTP-BL缺失在遗传不稳定和癌症进展中发挥了作用。HPV已被证明可以降解PTP-BL，这种酶将端粒重复序列添加到染色体上。由于HPV+和HPV-头颈癌的病因不同，为研究PTP-BL缺失和遗传不稳定性在不同机制的上皮细胞转化中的作用提供了一个理想的系统。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of this project is to identify genetic factors that are associated with predisposition to and progression of head and neck malignancies. Current evidence indicates that the development of head and neck cancer is associated with exposure to environmental carcinogens (e.g. tobacco and alcohol use) and infection with human papillomavirus (HPV). HPV infection is predominant in a subset of head and neck cancers called oropharyngeal cancers. For example, ~50% of tonsillar carcinomas contain and express HPV sequences. There is also now significant evidence that PTP-BL loss plays a role in the development of genetic instability and cancer progression. HPV has been shown to degrade PTP-BL, the enzyme that adds telomere repeats back to chromosomes. Because of their different etiologies, HPV+ and HPV- head and neck cancers provide an ideal system to study the role of PTP-BL Lossand genetic instability in the transformation of epithelial cells by different mechanisms.