Anaplasia & differentiation in a reversible cancer model

描述(申请人提供)：皮肤癌的可逆转基因小鼠模型将用于研究肿瘤和间变之间的关系，长期目标是更好地了解癌基因激活和失活对分化的影响。其具体目的是：1)验证肿瘤INV-MycERTM角质形成细胞在去除异位Myc功能后将分化的假设；2)确定c-MycERTM激活和随后失活时角质形成细胞基因表达的体内变化；3)设计一种普遍预期的、有条件表达的、可调控的c-Myc转基因小鼠。IHC和ISH将被用来评估INV-MycERTM角质形成细胞在SA1中的分化状态，而组织显微解剖和高通量芯片分析将确定Myc诱导SA2变化的转录基础。对于SA3，MycERTM转基因通过IRES连接到EGFP，并在其之前有一个带花的终止盒，将通过同源重组定位于一个普遍存在的活性位点。

DESCRIPTION (provided by applicant): A reversible transgenic mouse model for skin cancer will be used to investigate the relationship between neoplasia and anaplasia, with the long term goal of better understanding the consequences of oncogene activation and inactivation for differentiation. The specific aims are 1) to test the hypothesis that neoplastic INV-MycERTM keratinocytes will differentiate upon removal of ectopic Myc function; 2) to identify the in vivo alterations in keratinocyte gene expression upon activation and subsequent deactivation of c-MycERTM; 3) to engineer a ubiquitously prospective, conditionally expressed, regulatable c-Myc transgenic mouse. IHC and ISH will be employed to assess the differentiation state of INV-MycERTM keratinocytes in SA1 while tissue microdissection coupled with high throughput microarray analysis will define the transcriptional basis for Myc-induced change in SA2. For SA3, the MycERTM transgene, linked by way of an IRES to EGFP and preceded by a floxed Stop cassette, will be targeted to a ubiquitously active locus by homologous recombination.