Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product
Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product
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DOI：
10.1093/emboj/16.17.5310
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发表时间：
1997-09-01
期刊：
影响因子：
11.4
通讯作者：
Verde, P
中科院分区：
文献类型：
--
作者：
Vallone, D;Battista, S;Verde, P
先前表明高迁移率 I (HMGI)-C 染色质成分的表达对于逆转录病毒转化的甲状腺细胞系中肿瘤表型的建立至关重要。为了确定 HMGI-C 基因产物的可能靶标，我们分析了正常、完全转化和反义 HMGI-C 表达的大鼠甲状腺细胞中的 AP-1 复合物。我们发现肿瘤转化与 AP-1 活性的急剧增加有关，这反映了多种成分的变化。最强的效果是显着的 junB 和 fra-1 基因诱导，这在表达反义 HMGI-C 的细胞系中被阻止。这些结果表明HMGI-C基因产物对于与肿瘤转化相关的junB和fra-1转录诱导是必需的，通过用fra-1反义RNA载体稳定转染来抑制Fra-1蛋白合成可显着降低转化的甲状腺细胞的恶性表型，表明fra-1基因产物在细胞转化过程中的关键作用。
The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines, To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation, The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation.