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，利用基底细胞癌的ptch1小鼠模型作为与人类皮肤癌真正相关的强大研究工具，更广泛地研究皮肤生物学和肿瘤发生。这项应用是我们自己资助的关于小鼠基底细胞癌发生的研究的直接结果，以及在过去五年中发生的其他研究的洞察力。基于这些结果，我们在这里提出了一系列实验，旨在解决两个重要的问题--(I)BCC的起源细胞是什么？据我们所知，对于体内致癌过程中的任何癌症，这个问题都没有得到直接的和实验的回答。(Ii)基底细胞癌的细胞在自我更新能力上是异质性的吗？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够强大，足以回答这些问题，而且这些研究是如此相互关联，共同解决所有这些问题会产生真正的协同作用。我们之所以能够提出这些研究，是因为我们对基底细胞癌发生的长期兴趣和专业知识，尤其是因为刚刚出现的新技术和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.