Wasylyk C, Imler J L, Wasylyk B
Unité 184 INSERM, Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Stasbourg, France.
EMBO J. 1988 Aug;7(8):2475-83. doi: 10.1002/j.1460-2075.1988.tb03094.x.
The transcription factor PEA1 (a homologue of AP1 and c-jun) is highly active in several fibroblast cell lines, compared to its low activity in a myeloma and an embryo-carcinoma (EC) cell line. Serum components are essential to attain these high levels of PEA1 activity in fibroblasts. This serum requirement is abrogated by transformation with the oncogenes c-Ha-ras, v-src and polyoma middle T (Py-MT) but not by immortalization with polyoma large T (Py-LT), v-myc, c-myc or SV40 large T (SV40T). Expression in myeloma cells of the same transforming oncogenes, as well as v-mos and c-fos, activates PEA1, whereas expression of the same immortalizing oncogenes and EIA does not. These results suggest that a common target for transforming oncogenes is PEA1. Serum components have no effect on PEA1 activity in the myeloma and EC cell lines. In contrast, retinoic acid treatment of F9 EC cells augments PEA1 activity. These results suggest that transforming oncogene expression compensates for the absence of cell type-specific factors which are required to activate PEA1. Activation of PEA1 may lead to altered transcription of a set of transformation-related genes.
转录因子PEA1(AP1和c-jun的同源物)在几种成纤维细胞系中高度活跃,而在骨髓瘤细胞系和胚胎癌细胞系(EC)中活性较低。血清成分对于在成纤维细胞中达到这些高水平的PEA1活性至关重要。用癌基因c-Ha-ras、v-src和多瘤病毒中间T抗原(Py-MT)进行转化可消除这种血清需求,但用多瘤病毒大T抗原(Py-LT)、v-myc、c-myc或SV40大T抗原(SV40T)进行永生化处理则不会。在骨髓瘤细胞中表达相同的转化癌基因以及v-mos和c-fos可激活PEA1,而表达相同的永生化癌基因和EIA则不能。这些结果表明,转化癌基因的一个共同靶点是PEA1。血清成分对骨髓瘤细胞系和EC细胞系中的PEA1活性没有影响。相反,用视黄酸处理F9 EC细胞可增强PEA1活性。这些结果表明,转化癌基因的表达可补偿激活PEA1所需的细胞类型特异性因子的缺失。PEA1的激活可能导致一组与转化相关基因的转录改变。