Tumor-suppressive function of mutated gelsolin in ras-transformed cells.
Tumor-suppressive function of mutated gelsolin in ras-transformed cells.
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发表时间：
1993-09
期刊：
影响因子：
8
通讯作者：
L. Müllauer;H. Fujita;A. Ishizaki;N. Kuzumaki
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作者：
L. Müllauer;H. Fujita;A. Ishizaki;N. Kuzumaki
从人活化的Ha-ras癌基因转化的NIH3T3成纤维细胞(EJ-NIH3T3)中分离到的扁平逆转株R1表达肌动蛋白调节蛋白明胶蛋白的一个变体(p92-5.7)。我们已经克隆了编码p92-5.7的cDNA，并确定了p92-5.7表达的原因是密码子321的一个点突变，它导致氨基酸从脯氨酸变成组氨酸。为了解p92-5.7基因在ras转化细胞逆转中的作用，将编码p92-5.7基因的cDNA和人真核表达的明胶蛋白分别导入EJ-NIH3T3细胞。所有产生p92-5.7的转染体和产生人类正品明胶的三种转染体之一在同基因小鼠中要么丧失了致瘤性，要么降低了致瘤性。这些结果表明，突变的明胶蛋白可以抑制ras肿瘤，并表明如果表达水平增加，真正的明胶蛋白可能具有类似的抑制潜力。我们的数据表明，明胶蛋白在涉及哺乳动物ras原癌基因的细胞信号转导通路中发挥着重要作用。
The flat revertant R1, isolated from human activated Ha-ras oncogene-transformed NIH3T3 fibroblasts (EJ-NIH3T3), expresses a variant form of the actin-regulatory protein gelsolin (p92-5.7). We have cloned cDNAs encoding p92-5.7 and identified as the cause of the expression of p92-5.7 a point mutation in codon 321, which results in an amino acid change from proline to histidine. In order to understand the role of p92-5.7 in reversion of ras-transformed cells, cDNAs encoding p92-5.7 or human authentic gelsolin as a control were transfected into EJ-NIH3T3 cells. All the transfectants that produced p92-5.7 and one of three transfectants that produced human authentic gelsolin either lost or reduced tumorigenicity in syngeneic mice. These results demonstrate that mutated gelsolin can suppress a ras tumor and suggest that authentic gelsolin, if expressed at increased levels, may have a similar suppressive potential. Our data propose an important role for gelsolin in cellular signal transduction pathways that involve the mammalian ras proto-oncogene.