Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth.

Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth.
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DOI:
10.1111/j.1349-7006.1999.tb00733.x
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发表时间:
1999-03
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Sugiyama H
Sugiyama H
中科院分区:
其他
文献类型:
--
作者:
Oji Y;Ogawa H;Tamaki H;Oka Y;Tsuboi A;Kim EH;Soma T;Tatekawa T;Kawakami M;Asada M;Kishimoto T;Sugiyama H

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为了确定Wilms肿瘤基因WT 1在实体瘤的肿瘤发生中的作用,在34个实体瘤细胞系中检测了WT 1基因的表达(4个胃癌细胞系,5个结肠癌细胞系,15个肺癌细胞系,4个乳腺癌细胞系,1个生殖细胞肿瘤细胞系,2个卵巢癌细胞系,1个子宫癌细胞系,1个甲状腺癌细胞系,和一种肝细胞癌细胞系)。在4种胃癌细胞系中的3种、5种结肠癌细胞系中的全部、15种肺癌细胞系中的12种、4种乳腺癌细胞系中的2种、生殖细胞肿瘤细胞系、2种卵巢癌细胞系、子宫癌细胞系、甲状腺癌细胞系、肝细胞癌细胞系中检测到WT 1基因表达。因此,在检查的34个实体瘤细胞系中,28个(82%)表达WT 1。通过单链构象多态性分析,进一步分析了表达WT 1的三种细胞系(胃癌细胞系AZ-521、肺癌细胞系OS 3和卵巢癌细胞系TYK-nu)的WT 1基因突变和/或缺失。然而,在这三个细胞系中,在WT 1基因外显子1至外显子10的3/末端区域(WT 1基因由10个外显子组成)中未检测到突变或缺失。此外,当AZ-521、OS 3和TYK-nu细胞用WT 1反义寡聚体处理时,这些细胞的生长显著受到抑制,并伴有WT 1蛋白水平的降低。此外,转染的WT 1基因在癌细胞中的组成型表达抑制了WT 1反义寡聚体对细胞生长的反义作用。这些结果表明,WT 1基因在实体瘤的生长中起着重要作用,并且执行致癌基因而不是肿瘤抑制基因功能。
To determine the role of the Wilms' tumor gene WT1 in tumorigenesis of solid tumors, expression of the WT1 gene was examined in 34 solid tumor cell lines (four gastric cancer cell lines, five colon cancer cell lines, 15 lung cancer cell lines, four breast cancer cell lines, one germ cell tumor cell line, two ovarian cancer cell lines, one uterine cancer cell line, one thyroid cancer cell line, and one hepatocellular carcinoma cell line) by means of quantitative reverse transcriptase‐polymerase chain reaction. WT1 gene expression was detected in three of the four gastric cancer cell lines, all of the five colon cancer cell lines, 12 of the 15 lung cancer cell lines, two of the four breast cancer cell lines, the germ cell tumor cell line, the two ovarian cancer cell lines, the uterine cancer cell line, the thyroid cancer cell line, and the hepatocellular carcinoma cell line. Therefore, of the 34 solid tumor cell lines examined, 28 (82%) expressed WT1. Three cell lines expressing WT1 (gastric cancer cell line AZ‐521, lung cancer cell line OS3, and ovarian cancer cell line TYK‐nu) were further analyzed for mutations and/or deletions in the WT1 gene by means of single‐strand conformation polymorphism analysis. However, no mutations or deletions were detected in the region of the WT1 gene ranging from the 3/end of exon 1 to exon 10 (the WT1 gene consists of 10 exons) in these three cell lines. Furthermore, when AZ‐521, OS3, and TYK‐nu cells were treated with WT1 antisense oligomers, the growth of these cells was significantly inhibited in association with a reduction in WT1 protein levels. Furthermore, constitutive expression of the transfected WT1 gene in cancer cells inhibited the antisense effect of WT1 antisense oligomer on cell growth. These results indicated that the WT1 gene plays an essential role in the growth of solid tumors and performs an oncogenic rather than a tumor‐suppressor gene function.
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发表时间: 1974-01-01
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影响因子: --
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