肾母细胞瘤抑癌基因WT1抑制致瘤性乳腺上皮细胞的恶性进展。
The Wilms' tumor suppressor WT1 inhibits malignant progression of neoplastigenic mammary epithelial cells.
作者信息
Wang Lei, Wang Zhao-Yi
机构信息
Department of Surgery, Creighton University Medical School, Omaha, NE 68178, USA.
出版信息
Anticancer Res. 2008 Jul-Aug;28(4B):2155-60.
BACKGROUND
The Wilms' tumor suppressor gene, wt1, encodes a zinc-finger protein, WT1, that functions as a transcription regulator. Previous studies have suggested a contradictory role for WT1 in breast cancer development.
MATERIALS AND METHODS
MCF10AT3B cells, a cell line derived from a xenograft model of progressive human proliferative breast disease, were used to study WT1 function in early development of breast cancer. A stable cell line was established from MCF10AT3B cells that ectopically expressed the Wilms' tumor suppressor, WT1. Western blot analysis, in vitro and in vivo growth assays were used to study the effects of constitutive WT1 expression on malignant progression of MCF10AT3B cells.
RESULTS
WT1 expression had a profound effect on several aspects of the cell cycle machinery and inhibited estrogen-stimulated and nonstimulated cell growth in vitro. In nude mice, WT1 expression strongly suppressed estrogen-stimulated tumorigenesis of neoplastigenic MCF10AT3B cells.
CONCLUSION
WT1 plays an important role in maintaining normal growth of mammary epithelial cells and dysregulated WT1 expression may contribute to breast cancer development.
背景
肾母细胞瘤抑癌基因wt1编码一种锌指蛋白WT1，其作为转录调节因子发挥作用。先前的研究表明WT1在乳腺癌发展中具有矛盾的作用。
材料与方法
MCF10AT3B细胞系源自人类进行性增殖性乳腺疾病的异种移植模型，用于研究WT1在乳腺癌早期发展中的功能。从异位表达肾母细胞瘤抑癌基因WT1的MCF10AT3B细胞建立稳定细胞系。采用蛋白质免疫印迹分析、体外和体内生长试验来研究组成型WT1表达对MCF10AT3B细胞恶性进展的影响。
结果
WT1表达对细胞周期机制的多个方面有深远影响，并在体外抑制雌激素刺激和非刺激的细胞生长。在裸鼠中，WT1表达强烈抑制雌激素刺激的致瘤性MCF10AT3B细胞的肿瘤发生。
结论
WT1在维持乳腺上皮细胞的正常生长中起重要作用，WT1表达失调可能有助于乳腺癌的发展。
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