Seth A, Papas T S
National Cancer Institute, Laboratory of Molecular Oncology, Frederick, Maryland 21702-1201.
Oncogene. 1990 Dec;5(12):1761-7.
The proto-oncogene ets-1 is a member of the ets family of genes that share homology with the viral oncogene, v-ets, of the avian leukemia virus E26. By using expression vectors, we demonstrate that the ets-1 gene transforms NIH3T3 cells and the ets-1 transfected cells form colonies in soft agar and induce tumors in nude mice. We have also determined that the ets-1 protein contains homology with the helix-loop-helix motif of the HLH family proteins, but lacks the basic domain upstream of helix I. Transfection of the NIH3T3 cells with ets-1 vectors results in the activation of the endogenous ets-1 gene. Using hybridization probes that can distinguish between transcripts from endogenous and exogenous templates, we show that the endogenous ets-1 gene is activated by the expression of the transfected exogenous ets-1. In contrast, the expression of transfected ets-2 has no effect on the endogenous ets-1 gene expression. The results indicate that the ets-1 proto-oncogene is positively autoregulated by its product.
原癌基因ets-1是ets基因家族的成员之一，该家族与禽白血病病毒E26的病毒癌基因v-ets具有同源性。通过使用表达载体，我们证明ets-1基因可转化NIH3T3细胞，并且ets-1转染细胞可在软琼脂中形成集落并在裸鼠中诱发肿瘤。我们还确定ets-1蛋白与HLH家族蛋白的螺旋-环-螺旋基序具有同源性，但在螺旋I上游缺乏碱性结构域。用ets-1载体转染NIH3T3细胞会导致内源性ets-1基因的激活。使用能够区分内源性和外源性模板转录本的杂交探针，我们表明转染的外源性ets-1的表达可激活内源性ets-1基因。相比之下，转染的ets-2的表达对内源性ets-1基因表达没有影响。结果表明，ets-1原癌基因受其产物正向自我调节。
