Biology of Basal Cell Carcinomas

描述（由申请人提供）：该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Ptch1小鼠BCC癌变模型作为与人类皮肤癌真正相关的强大研究工具，更广泛地用于皮肤生物学和肿瘤发生。这一应用是我们自己的nih资助的研究的直接结果，这些研究是在这些小鼠中进行的BCC致癌作用，也是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旨在解决两个重要问题的实验：(i) bcc的起源细胞是什么？这是一个问题，据我们所知，还没有直接回答和实验对任何癌症的体内致癌过程（ii）的细胞是异质的自我更新的能力吗？我们提出了一系列雄心勃勃的研究，这些研究的范围与这些问题相称，我们相信这些研究有足够的力量来回答这些问题，而且这些研究是如此相互关联，以至于在一起解决所有这些问题时会产生真正的协同作用。我们之所以能够提出这些研究，是因为我们在BCC癌变方面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.