Gene trapping identifies inhibitors of oncogenic transformation -: The tissue inhibitor of metalloproteinases-3 (TIMP3) and collagen type I α2 (COL1A2) are epidermal growth factor-regulated growth repressors
Gene trapping identifies inhibitors of oncogenic transformation -: The tissue inhibitor of metalloproteinases-3 (TIMP3) and collagen type I α2 (COL1A2) are epidermal growth factor-regulated growth repressors
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DOI：
10.1074/jbc.273.22.13848
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发表时间：
1998-05-29
影响因子：
4.8
通讯作者：
von Melchner, H
中科院分区：
文献类型：
--
作者：
Andreú, T;Beckers, T;von Melchner, H
已使用基因陷阱策略来鉴定在由活化的表皮生长因子（EGF）/EGF受体信号转导途径转化的细胞中被抑制的基因，用含有人CD 2抗原和U3区分泌的碱性磷酸酶的编码序列的逆转录病毒感染表达EGF受体的NIH 3 T3细胞（HER 1细胞）。通过选择和反对CD 2表达，我们获得了克隆，其中基因陷阱已整合到基因选择性抑制EGF。其中两个克隆编码分泌的细胞外基质蛋白TIMP 3和COL 1A 2，我们在这里表明，这两个基因是RAS的下游靶点，并被EGF诱导的转化特异性抑制。此外，这种策略在正常染色体位置标记肿瘤抑制基因，从而改善靶向特异性筛选抗肿瘤药物。
A gene trap strategy has been used to identify genes that are repressed in cells transformed by an activated epidermal growth factor (EGF)/EGF receptor signal transduction pathway, EGF receptor expressing NIH3T3 cells (HER1 cells) were infected with a retrovirus containing coding sequences for the human CD2 antigen and for secreted alkaline phosphatase in the U3 region. By selecting for and against CD2 expression, we obtained clones in which the gene trap had integrated into genes selectively repressed by EGF. Two of these clones encoded for the secreted extracellular matrix proteins TIMP3 and COL1A2, We show here that both genes are downstream targets of RAS and are specifically repressed by EGF-induced transformation. Moreover, this strategy tags tumor suppressor genes in their normal chromosomal location, thereby improving target-specific screens for antineoplastic drugs.