Cantalupo Paul G, Sáenz-Robles Maria Teresa, Rathi Abhilasha V, Beerman Rebecca W, Patterson William H, Whitehead Robert H, Pipas James M
Department of Biological Sciences, 559 Crawford Hall, University of Pittsburgh Pittsburgh, Pennsylvania 15260, USA.
Virology. 2009 Mar 30;386(1):183-91. doi: 10.1016/j.virol.2008.12.038. Epub 2009 Feb 8.
SV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examined global gene expression in SV40-transformed mouse embryo fibroblasts, and in enterocytes obtained from transgenic mice. SV40 transformation alters the expression of approximately 800 cellular genes in both systems. Much of this regulation is observed in both MEFs and enterocytes and is consistent with T antigen action on the Rb-E2F pathway. However, the regulation of many genes is cell-type specific, suggesting that unique signaling pathways are activated in different cell types upon transformation, and that the consequences of SV40 transformation depends on the type of cell targeted.
SV40通过两种癌蛋白——大T抗原和小t抗原的作用来转化细胞。小t抗原作用于磷酸酶PP2A，而大T抗原通过作用于多种蛋白质（包括肿瘤抑制因子Rb和p53）来刺激细胞增殖和存活。大T抗原还结合转录起始复合物的成分和几种转录因子。我们检测了SV40转化的小鼠胚胎成纤维细胞以及从转基因小鼠获得的肠上皮细胞中的全基因组表达。在这两个系统中，SV40转化改变了大约800个细胞基因的表达。这种调控在很大程度上在小鼠胚胎成纤维细胞和肠上皮细胞中都能观察到，并且与T抗原对Rb-E2F途径的作用一致。然而，许多基因的调控具有细胞类型特异性，这表明在转化后不同细胞类型中独特的信号通路被激活，并且SV40转化的后果取决于所靶向的细胞类型。
