WT1-MEDIATED GROWTH SUPPRESSION OF WILMS-TUMOR CELLS EXPRESSING A WT1 SPLICING VARIANT
WT1-MEDIATED GROWTH SUPPRESSION OF WILMS-TUMOR CELLS EXPRESSING A WT1 SPLICING VARIANT
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DOI：
10.1126/science.8266105
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发表时间：
1993-12-24
期刊：
影响因子：
56.9
通讯作者：
GARVIN, AJ
中科院分区：
文献类型：
--
作者：
HABER, DA;PARK, S;GARVIN, AJ
一种人类肾母细胞瘤细胞系（RM1）被开发来测试WT1的肿瘤抑制活性，WT1是锌指转录因子，在发育中的人类肾脏中表达，在肾母细胞瘤的一个亚群中突变失活。转染四种野生型WT1亚型均可抑制RM1细胞的生长。这些细胞中的内源性WT1转录本缺乏外显子2序列，这是一种剪接改变，在所有Wilms肿瘤中也检测到不同数量的剪接改变，但在正常肾脏中没有。这种编码功能改变蛋白的异常转录产物的产生可能代表了Wilms肿瘤中WT1失活的独特机制。
A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally inactivated in a subset of Wilms tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth of RM1 cells. The endogenous WT1 transcript in these cells was devoid of exon 2 sequences, a splicing alteration that was also detected in varying amounts in all Wilms tumors tested but not in normal kidney. Production of this abnormal transcript, which encodes a functionally altered protein, may represent a distinct mechanism for inactivating WT1 in Wilms tumors.