Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation
Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation
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DOI：
10.1073/pnas.96.24.14037
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发表时间：
1999-11-23
影响因子：
11.1
通讯作者：
Colburn, NH
中科院分区：
文献类型：
--
作者：
Cmarik, JL;Min, HZ;Colburn, NH
小鼠JB6促进敏感（P+）和-耐药（P-）细胞的mRNA差异显示比较发现了一种抑制肿瘤转化的新基因产物。JB6 P+和P-细胞是对肿瘤启动子的转化反应不同的遗传变异；P+细胞形成不依赖于锚定的集落，具有致瘤性，而P细胞则没有。一个不同显示的碎片，A7-1。在P细胞中优先表达的水平大于或等于P+细胞的10倍，使其mRNA成为肿瘤转化的候选抑制剂。分离到与小鼠Pdcd4基因cDNA相同的A7-1 cDNA。也被称为MA-3或TIS，类似于人类H731和197/15a。到目前为止，Pdcd4蛋白的功能尚不清楚。与mRNA水平相似，P-细胞的Pdcd4蛋白水平高于P+细胞。Pdcd4 mRNA在另一个小鼠皮肤肿瘤进展系列中进展较慢的角化细胞中表达水平也较高。为了验证Pdcd4抑制肿瘤启动子诱导转化的假设，从亲代P细胞中产生了表达反义Pdcd4的稳定细胞系。在反义细胞系中Pdcd4蛋白的减少伴随着转化敏感（Pf）表型的获得。通过过表达Pdcd4感觉片段，反义转染的细胞恢复到其初始p表型。这些观察结果表明，Pdcd4蛋白抑制肿瘤转化。
An mRNA differential display comparison of mouse JB6 promotion-sensitive (P+) and -resistant (P-) cells identified a novel gene product that inhibits neoplastic: transformation. The JB6 P+ and P- cells are genetic variants that differ in their transformation response to tumor promoters; P+ cells form anchorage-independent colonies that are tumorigenic, and P- cells do not. A differentially displayed fragment, A7-1. was preferentially expressed in P- cells at levels greater than or equal to 10-fold those in P+ cells, making its mRNA a candidate inhibitor of neoplastic transformation. An A7-1 cDNA was isolated that was identical to murine Pdcd4 gene cDNAs. also known as MA-3 or TIS,and analogous to human H731 and 197/15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P- than in P+ cells. Pdcd4 mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisense Pdcd4 were generated from parental P- cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (Pf) phenotype. The antisense-transfected cells were reverted to their initial P-phenotype by overexpression of a Pdcd4 sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation.