Klein Andreas, Guhl Eva, Zollinger Raphael, Tzeng Yin-Jeh, Wessel Ralf, Hummel Michael, Graessmann Monika, Graessmann Adolf
Institut für Molekularbiologie und Bioinformatik, Charité Hospital, Campus Benjamin Franklin, Universitätsmedizin Berlin, Arnimallee 22, 14195 Berlin, Germany.
J Mol Med (Berl). 2005 May;83(5):362-76. doi: 10.1007/s00109-004-0625-1. Epub 2005 Jan 21.
Microarray studies revealed that as a first hit the SV40 T/t antigen causes deregulation of 462 genes in mammary gland cells (ME cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell proliferation specific and Rb-E2F dependent, causing ME cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal ME cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal ME cells. The profile of retransformants shows that only 38 deregulated genes are tumor-specific, and that none of them is considered to be a typical breast cancer gene.
微阵列研究表明,作为第一步,SV40 T/t抗原导致WAP-SVT/t转基因动物乳腺细胞(ME细胞)中462个基因的表达失调。大多数失调基因是细胞增殖特异性的且依赖Rb-E2F,导致ME细胞增殖和腺体增生,但不会形成乳腺癌。在乳腺肿瘤细胞中,另有207个基因差异表达,其中大多数属于细胞通讯类别。在组织培养中,乳腺肿瘤细胞经常关闭WAP-SVT/t转基因表达,并恢复正常ME细胞的形态和生长特征,尽管肿瘤回复细胞是非整倍体,只有114个基因恢复到正常ME细胞的表达水平。再转化体的图谱显示,只有38个失调基因是肿瘤特异性的,而且其中没有一个被认为是典型的乳腺癌基因。