Anaplasia & differentiation in a reversible cancer model

描述（由申请方提供）：将使用皮肤癌的可逆转基因小鼠模型研究瘤形成和间变性之间的关系，长期目标是更好地了解癌基因激活和失活对分化的影响。具体目的是：1）检验肿瘤性INV-MycER ™角质形成细胞在去除异位Myc功能后将分化的假设; 2）鉴定c-MycER ™激活和随后失活后角质形成细胞基因表达的体内变化; 3）设计一种普遍存在的前瞻性、条件表达、可调控的c-Myc转基因小鼠。将采用IHC和ISH评估SA 1中INV-MycER ™角质形成细胞的分化状态，而组织显微切割结合高通量微阵列分析将确定SA 2中Myc诱导变化的转录基础。对于SA 3，MycER ™转基因通过IRES与EGFP连接，并在其之前有一个floxed Stop盒，将通过同源重组靶向一个普遍存在的活性基因座。

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.