Restriction landmark genomic scanning of mouse liver tumors for gene amplification: overexpression of cyclin A2.
Restriction landmark genomic scanning of mouse liver tumors for gene amplification: overexpression of cyclin A2.
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小鼠肝脏肿瘤的限制性标志基因组扫描以进行基因扩增：细胞周期蛋白 A2 的过度表达。
DOI：
10.1006/bbrc.2000.3124
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Held,WA
中科院分区：
文献类型：
--
作者：
Haddad,R;Morrow,AD;Plass,C;Held,WA
用限制性标记基因组扫描（RLGS）分析SV 40 T/t抗原诱导的转基因小鼠肝肿瘤。使用NotI作为限制性标志，RLGS靶向基因组中基因丰富区域中发现的CpG岛。由于许多RLGS标志被映射，候选基因方法可以用于帮助确定哪些基因在肿瘤中被改变。RLGS分析显示一个肿瘤特异性扩增图谱接近CcnA 2（细胞周期蛋白A2）和Fgf 2（成纤维细胞生长因子2）。Southern分析证实，这两个癌基因扩增在这个肿瘤和第二个，独立的肝肿瘤。Fgf 2 RNA在肿瘤中检测不到，而CcnA 2 RNA和细胞周期蛋白A2蛋白分别在25%和50%的肿瘤中过表达。结合RLGS与候选基因的方法表明，细胞周期蛋白A2扩增和过表达是一个可能的选择性事件在转基因小鼠肝肿瘤。我们的研究结果还表明，我们的小鼠肝肿瘤发生的小鼠模型准确地概括了在人肝细胞癌中观察到的事件。
SV40 T/t antigen-induced liver tumors from transgenic mice were analyzed by Restriction Landmark Genomic Scanning (RLGS). Using NotI as the restriction landmark, RLGS targets CpG islands found in gene-rich regions of the genome. Since many RLGS landmarks are mapped, the candidate gene approach can be used to help determine which genes are altered in tumors. RLGS analysis revealed one tumor-specific amplification mapping close to CcnA2 (cyclin A2) and Fgf2 (fibroblast growth factor 2). Southern analysis confirmed that both oncogenes are amplified in this tumor and in a second, independent liver tumor. Whereas Fgf2 RNA is undetectable in tumors, CcnA2 RNA and cyclin A2 protein was overexpressed in 25 and 50% of tumors, respectively. Combining RLGS with the candidate gene approach indicates that cyclin A2 amplification and overexpression is a likely selected event in transgenic mouse liver tumors. Our results also indicate that our mouse model for liver tumorigenesis in mice accurately recapitulates events observed in human hepatocellular carcinoma.