Geerts Dirk, Schilderink Nathalie, Jorritsma Gerda, Versteeg Rogier
Department of Human Genetics M1-159, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Cancer Lett. 2003 Jul 18;197(1-2):87-92. doi: 10.1016/s0304-3835(03)00087-9.
We recently found amplification of the TALE homeobox gene MEIS1 in the IMR32 neuroblastoma cell line. We now demonstrate high-level expression of the MEIS1 and MEIS2 genes, as well as efficient expression of most other TALE family member genes in a panel of neuroblastoma cell lines. Stable transfection of MEIS1-expressing cell lines with cDNA encoding a naturally occurring dominant-negative splice variant of MEIS1 (MEIS1E) yielded clones with impaired cell proliferation, gain of differentiated phenotype, and increased contact inhibition and cell death. This indicated a relevance of MEIS expression for neuroblastoma cell growth and proliferation. We therefore determined the gene expression profiles of several MEIS1E transfectants using serial analysis of gene expression (SAGE). A large number of genes showed differential expression as a result of MEIS1E expression. These include genes involved in developmental signalling pathways, chromatin binding, cell cycle control, proliferation, and apoptosis. The results presented provide important clues for the oncogenic function of MEIS1 in neuroblastoma.
我们最近在IMR32神经母细胞瘤细胞系中发现了TALE同源框基因MEIS1的扩增。我们现在证明了MEIS1和MEIS2基因的高水平表达，以及在一组神经母细胞瘤细胞系中大多数其他TALE家族成员基因的有效表达。用编码MEIS1天然存在的显性负性剪接变体（MEIS1E）的cDNA对表达MEIS1的细胞系进行稳定转染，得到了细胞增殖受损、分化表型增加、接触抑制和细胞死亡增加的克隆。这表明MEIS表达与神经母细胞瘤细胞生长和增殖相关。因此，我们使用基因表达序列分析（SAGE）确定了几个MEIS1E转染子的基因表达谱。大量基因因MEIS1E表达而表现出差异表达。这些基因包括参与发育信号通路、染色质结合、细胞周期控制、增殖和凋亡的基因。所呈现的结果为MEIS1在神经母细胞瘤中的致癌功能提供了重要线索。
