Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer
Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer
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DOI：
10.1073/pnas.94.15.8132
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发表时间：
1997-07-22
影响因子：
11.1
通讯作者：
Daniel, CW
中科院分区：
文献类型：
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作者：
Silberstein, GB;VanHorn, K;Daniel, CW
WT1 Wilms肿瘤抑制基因的产物控制编码胰岛素样生长因子和转化生长因子β信号系统的基因的表达，这些生长因子在乳腺肿瘤生长中的作用使我们研究WT1基因在正常和癌性乳腺组织中的可能表达，通过免疫组织化学检测WT1在正常乳腺导管和小叶中的表达，在对21例浸润性肿瘤的调查中，40%完全缺乏免疫检测的WT1，另外28%主要为WT1阴性。在一些肿瘤细胞中发现了WT 1的胞浆定位，但未发现核定位。高水平，在更晚期的雌激素受体阴性肿瘤中，在这种高度恶性的亚群中，有时也检测到可以与WT1物理相互作用的肿瘤抑制蛋白p53，在正常和肿瘤组织中通过逆转录偶联PCR检测到WT1 mRNA，WT1 mRNA的选择性剪接可以通过改变其调节结构域或锌指结构域来调节WT1蛋白的基因靶向，在乳腺癌患者的随机样本中，WT1 mRNA剪接变体的相对比例发生了改变，这提供了证据，表明不同的肿瘤mag具有共同的WT1相关缺陷，导致靶基因的调节改变。
The product of the WT1 Wilms tumor suppressor gene controls the expression of genes encoding components of the insulin-like growth factor and transforming growth factor beta signaling systems, The role of these growth factors in breast tumor growth led us to investigate possible WT1 gene expression in normal and cancerous breast tissue, WT1 was detected by immunohistochemistry in the normal mammary duct and lobule, and the patterns of expression were consistent with developmental regulation, In a survey of 21 infiltrating tumors, 40% lacked immunodetectable WT1 altogether and an additional 28% were primarily WT1-negative. Cytoplasmic, but not nuclear, localization of WT1 was noted in some tumor cells and WT1 mas detected, sometimes at. high levels, in more-advanced estrogen-receptor-negative tumors, In this highly malignant subset, the tumor suppressor protein p53, which can physically interact with WT1, was also sometimes detected, WT1 mRNA was detected in normal and tumor tissue bg reverse transcription-coupled PCR, Alternative splicing of the WT1 mRNA may regulate gene targeting of the WT1 protein through changes either in its regulatory or zinc-finger domains, The relative proportions of WT1 mRNA splice variants were altered in a random sample of breast tamers, providing evidence that different tumors mag share a common WT1-related defect resulting in altered regulation of target genes.