Biology of Basal Cell Carcinomas

描述（由申请人提供）：本项目的目标是更好地了解基底细胞癌（BCC）与组织干细胞的关系，利用BCC致癌作用的Ptch 1小鼠模型作为与人类皮肤癌以及更广泛的皮肤生物学和肿瘤发生真实的相关性的强大研究工具。这项应用是我们自己的NIH资助的研究BCC在这些小鼠中的致癌作用的直接产物，以及在过去五年中发生的其他人的见解。基于这些结果，我们在此提出了一组实验，旨在解决两个重要的问题-（i）什么是BCC的起源细胞？这是一个问题，据我们所知，还没有回答直接和实验的任何癌症的致癌过程在体内（ii）是细胞的基底细胞癌异质性在其自我更新的能力？我们提出了一套雄心勃勃的研究，其范围与这些问题相称，我们相信这些研究足以回答这些问题，而且这些研究相互关联，在一起解决所有问题时会产生真实的协同作用。我们能够提出这些研究，是因为我们对BCC致癌作用的长期兴趣和专业知识，特别是因为新技术和新方法首次使这些研究成为可能。

DESCRIPTION (provided by applicant): The goal of this Project is the better understanding of the relationship of basal cell carcinomas (BCCs) to tissue stem cells, utilizing the Ptch1 mouse model of BCC carcinogenesis as a robust research tool of real relevance to human skin cancer and more broadly to skin biology and tumorigenesis. This application is a direct outgrowth of our own NIH-funded studies of BCC carcinogenesis in these mice as well as of the insights of others that have occurred during the past half-decade. Based on these results we propose herein a set of experiments designed to address two important questions - (i) What is the cell of origin of BCCs? This is a question which, to our knowledge, has not been answered directly and experimentally for any cancer for the carcinogeneic process in vivo (ii) Are the cells of a BCC heterogeneous in their capacity for self-renewal? We propose a set of ambitious studies which are of a scope commensurate with these questions, which we are confident are sufficiently powerful to answer the questions, and which are so inter-related that there is a real synergy in addressing all of them together. We are able to propose these studies because of our long-standing interest and expertise in BCC carcinogenesis and, especially, because new techniques and approaches just now for the first time make these studies possible.