Cheng Andy J, Cheng Ngan Ching, Ford Jette, Smith Janice, Murray Jayne E, Flemming Claudia, Lastowska Maria, Jackson Michael S, Hackett Christopher S, Weiss William A, Marshall Glenn M, Kees Ursula R, Norris Murray D, Haber Michelle
Children's Cancer Institute Australia for Medical Research, P.O. Box 81, Randwick, 2031 Sydney, Australia.
Eur J Cancer. 2007 Jun;43(9):1467-75. doi: 10.1016/j.ejca.2007.03.008. Epub 2007 Apr 20.
Overexpression of the human MYCN oncogene driven by a tyrosine hydroxylase promoter causes tumours in transgenic mice that recapitulate the childhood cancer neuroblastoma. To establish an in vitro model to study this process, a series of isogenic cell lines were developed from these MYCN-driven murine tumours. Lines were established from tumours arising in homozygous and hemizygous MYCN transgenic mice. Hemizygous tumours gave rise to cell lines growing only in suspension. Homozygous tumours gave rise to similar suspension lines as well as morphologically distinct substrate-adherent lines characteristic of human S-type neuroblastoma cells. FISH analysis demonstrated selective MYCN transgene amplification in cell lines derived from hemizygous mice. Comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) analysis confirmed a range of neuroblastoma-associated genetic changes in the various lines, in particular, gain of regions syntenic with human 17q. These isogenic lines together with the transgenic mice thus represent valuable models for investigating the biological characteristics of aggressive neuroblastoma.
由酪氨酸羟化酶启动子驱动的人类MYCN癌基因过表达会在转基因小鼠中引发肿瘤，这些肿瘤重现了儿童癌症神经母细胞瘤的特征。为了建立一个体外模型来研究这一过程，从这些由MYCN驱动的小鼠肿瘤中培育出了一系列同基因细胞系。细胞系是从纯合和半合子MYCN转基因小鼠产生的肿瘤中建立的。半合子肿瘤产生的细胞系只能在悬浮状态下生长。纯合子肿瘤产生了类似的悬浮细胞系以及形态上不同的贴壁细胞系，这些细胞系具有人类S型神经母细胞瘤细胞的特征。荧光原位杂交（FISH）分析表明，在源自半合子小鼠的细胞系中存在选择性MYCN转基因扩增。比较基因组杂交（CGH）和荧光原位杂交（FISH）分析证实，各个细胞系中存在一系列与神经母细胞瘤相关的基因变化，特别是与人类17q同线的区域增加。因此，这些同基因细胞系与转基因小鼠一起代表了研究侵袭性神经母细胞瘤生物学特性的宝贵模型。
