肾母细胞瘤1蛋白的下调抑制乳腺癌增殖。

Downregulation of Wilms' tumor 1 protein inhibits breast cancer proliferation.

作者信息

Zapata-Benavides Pablo, Tuna Musaffe, Lopez-Berestein Gabriel, Tari Ana M

机构信息

Department of Bioimmunotherapy, Section of Immunobiology and Drug Carriers, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 422, Houston, TX 77030, USA.

出版信息

Biochem Biophys Res Commun. 2002 Jul 26;295(4):784-90. doi: 10.1016/s0006-291x(02)00751-9.

DOI:10.1016/s0006-291x(02)00751-9

PMID:12127961

Abstract

High levels of Wilms' Tumor 1 (WT1) mRNA have been correlated with poor prognosis in breast cancer patients. However, the function of WT1 protein in breast cancer is not known. We observed that the levels of WT1 protein correlated with the proliferation of breast cancer cells. When the proliferation of breast cancer cells was stimulated by 17beta-estradiol, WT1 protein expression increased. But when the proliferation of breast cancer cells was inhibited by tamoxifen or all-trans retinoic acid (ATRA), WT1 protein expression decreased. We hypothesize that WT1 protein plays a role in regulating breast cancer cell proliferation. Using liposome-incorporated WT1 antisense oligodeoxynucleotides, we found that downregulation of WT1 protein expression led to breast cancer growth inhibition and reduced cyclin D1 protein levels. These results indicate that WT1 protein contributes to breast cancer progression by promoting breast cancer cell proliferation.

摘要

高水平的威尔姆斯瘤1（WT1）信使核糖核酸（mRNA）与乳腺癌患者的不良预后相关。然而，WT1蛋白在乳腺癌中的功能尚不清楚。我们观察到WT1蛋白水平与乳腺癌细胞的增殖相关。当乳腺癌细胞的增殖受到17β-雌二醇刺激时，WT1蛋白表达增加。但当乳腺癌细胞的增殖受到他莫昔芬或全反式维甲酸（ATRA）抑制时，WT1蛋白表达下降。我们推测WT1蛋白在调节乳腺癌细胞增殖中起作用。使用脂质体包裹的WT1反义寡脱氧核苷酸，我们发现WT1蛋白表达的下调导致乳腺癌生长受抑制，并降低细胞周期蛋白D1蛋白水平。这些结果表明，WT1蛋白通过促进乳腺癌细胞增殖而有助于乳腺癌进展。