Murphy Daniel J, Swigart Lamorna Brown, Israel Mark A, Evan Gerard I
Cancer Research Institute, University of California at San Francisco, San Francisco, California 94143-0875, USA.
Mol Cell Biol. 2004 Mar;24(5):2083-90. doi: 10.1128/MCB.24.5.2083-2090.2004.
We have previously described a transgenic mouse model of epidermal neoplasia wherein expression of a switchable form of c-Myc, MycER(TAM), is targeted to the postmitotic suprabasal keratinocytes of murine epidermis via the involucrin promoter. Sustained activation of c-MycER(TAM) results in a progressive neoplastic phenotype characterized by aberrant ectopic proliferation and delayed differentiation of suprabasal keratinocytes, culminating in papillomatosis. Transcription of the Id2 gene is regulated by Myc family proteins. Moreover, Id2 is implicated as a pivotal determinant of cell fate in multiple lineages and has a demonstrated role in mediating Myc-dependent cell proliferation in vitro through its interaction with retinoblastoma protein. Using Id2 nullizygous mice, we assessed in vivo the requirement for Id2 in mediating Myc-induced papilloma formation in skin. We show that absence of Id2 has no discernible impact on any measurable attribute of Myc function or on the timing or extent of eventual tumor formation. Thus, our data argue against any essential role for Id2 in mediating Myc action in vivo.
我们之前描述过一种表皮肿瘤形成的转基因小鼠模型，其中可转换形式的c-Myc，即MycER(TAM)，通过内披蛋白启动子靶向于小鼠表皮有丝分裂后的基底层上的角质形成细胞。c-MycER(TAM)的持续激活会导致一种渐进性肿瘤表型，其特征为基底层上的角质形成细胞异常异位增殖和分化延迟，最终导致乳头瘤病。Id2基因的转录受Myc家族蛋白调控。此外，Id2被认为是多个谱系中细胞命运的关键决定因素，并且通过与视网膜母细胞瘤蛋白相互作用，在体外介导Myc依赖性细胞增殖中发挥作用。利用Id2基因敲除小鼠，我们在体内评估了Id2在介导Myc诱导的皮肤乳头瘤形成中的必要性。我们发现，Id2的缺失对Myc功能的任何可测量属性、最终肿瘤形成的时间或程度均无明显影响。因此，我们的数据表明Id2在体内介导Myc作用方面不发挥任何重要作用。
