Haupt Y, Alexander W S, Barri G, Klinken S P, Adams J M
Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, Australia.
Cell. 1991 May 31;65(5):753-63. doi: 10.1016/0092-8674(91)90383-a.
To search for genes that can collaborate with myc in lymphomagenesis, we exploited retroviral insertional mutagenesis in E mu-myc transgenic mice. Moloney murine leukemia virus accelerated development of B lymphoid tumors. Three quarters contained a provirus within the known pim-1 or pim-2 loci, new loci bmi-1 and emi-1, or combinations of these. bmi-1 insertions predominated, occurring in half the tumors, and resulted in elevated bmi-1 mRNA levels. Significantly, the bmi-1 gene, which is expressed in diverse normal cells, encodes a Cys/His metal-binding motif (C3HC4) that resembles those in several DNA-binding proteins and defines a new category of zinc finger gene. Thus, myc-induced lymphomagenesis can entail the concerted action of several genes, including the presumptive nuclear regulator bmi-1.
为了寻找在淋巴瘤发生过程中能与myc协同作用的基因，我们利用逆转录病毒插入诱变技术在Eμ-myc转基因小鼠中进行研究。莫洛尼鼠白血病病毒加速了B淋巴细胞肿瘤的发展。四分之三的肿瘤在已知的pim-1或pim-2基因座、新的基因座bmi-1和emi-1内含有前病毒，或这些基因座的组合。bmi-1插入占主导，出现在一半的肿瘤中，并导致bmi-1 mRNA水平升高。值得注意的是，在多种正常细胞中表达的bmi-1基因编码一个Cys/His金属结合基序（C3HC4），该基序类似于几种DNA结合蛋白中的基序，并定义了一类新的锌指基因。因此，myc诱导的淋巴瘤发生可能需要几个基因的协同作用，包括假定的核调节因子bmi-1。
