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阴阳-1 抑制肿瘤细胞生长,并抑制 CDK4 和细胞周期蛋白 D1 与 p21WAF1/Cip1 复合物的形成。

Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1.

机构信息

Centre for Vascular Research, University of New South Wales, Sydney, Australia.

出版信息

Int J Oncol. 2012 May;40(5):1575-80. doi: 10.3892/ijo.2012.1362. Epub 2012 Feb 9.

DOI:10.3892/ijo.2012.1362
PMID:22322893
Abstract

The GLI-Krüppel zinc finger factor yin yang-1 (YY1) is a complex protein that regulates a variety of processes including transcription, proliferation, development and differentiation. YY1 inhibits cell growth in a cell type-specific manner. The role played by YY1 in its control of tumor cell growth is unclear and controversial. We show here that YY1 can suppress the growth of different tumor cell types in vitro, including human breast carcinoma cells and glioblastoma cells. YY1 also blocked the growth of 13762 MAT mammary adenocarcinoma isografts in rats. YY1 inhibited 13762 MAT tumor growth by approximately 80% compared with the GFP alone group 21 days after injection. YY1 inhibited proliferating cell nuclear antigen (PCNA) expression and pRbSer249/Thr252 phosphorylation without influencing tumor microvascular density. Moreover, YY1 inhibited p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. These findings demonstrate that YY1 can negatively regulate the growth of multiple malignant cell types.

摘要

GLI-Krüppel 锌指因子 yin yang-1(YY1)是一种复杂的蛋白质,可调节包括转录、增殖、发育和分化在内的多种过程。YY1 以细胞类型特异性的方式抑制细胞生长。YY1 在其对肿瘤细胞生长的控制中的作用尚不清楚且存在争议。我们在此表明,YY1 可以体外抑制不同肿瘤细胞类型的生长,包括人乳腺癌细胞和神经胶质瘤细胞。YY1 还阻止了大鼠中 13762 MAT 乳腺腺癌同种移植物的生长。与单独注射 GFP 组相比,注射后 21 天,YY1 抑制了 13762 MAT 肿瘤的生长,抑制率约为 80%。YY1 抑制了增殖细胞核抗原(PCNA)的表达和 pRbSer249/Thr252 磷酸化,而不影响肿瘤微血管密度。此外,YY1 抑制了 p21WAF1/Cip1 复合物与 CDK4 和 cyclin D1 的形成。这些发现表明 YY1 可以负调控多种恶性细胞类型的生长。

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