Transcriptional repression of MMP-1 by p21SNFT and reduced in vitro invasiveness of hepatocarcinoma cells
Transcriptional repression of MMP-1 by p21SNFT and reduced in vitro invasiveness of hepatocarcinoma cells
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DOI：
10.1038/sj.onc.1208109
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发表时间：
2004-11-18
期刊：
影响因子：
8
通讯作者：
McGuire, KL
中科院分区：
文献类型：
--
作者：
Bower, KE;Fritz, JM;McGuire, KL
p21（SNFT）（从T细胞分离的21 kDa小核因子）是人碱性亮氨酸拉链转录因子，其可以抑制AP-1介导的转录。我们在这里表明，p21（SNFT）在HepG 2细胞中的过度表达导致基质金属蛋白酶-1的抑制70- 80%。p21（SNFT）在基质金属蛋白酶-1启动子-88 Ets/AP-1增强子元件处与Jun相互作用，其中已知Jun通过与Fos和Ets蛋白相互作用来激活转录。当p21（SNFT）/六月二聚体绑定的元素中存在的Ets，DNA的保护不同于Fos时，与六月配对。数据表明，在整体构象之间的差异p21（SNFT）-含和Fos-含复合物，可能参与的抑制基质金属蛋白酶-1（SNFT）的p21。p21（SNFT）的过表达导致HepG 2细胞通过I型胶原和重建基底膜的侵袭性降低，这种效果类似于通过直接免疫耗竭基质金属蛋白酶-1获得的效果。结果表明，抑制基质金属蛋白酶-1（SNFT）的机制可能是利用抑制病理性基质重塑在体内癌症的进展。
p21(SNFT) (21 kDa small nuclear factor isolated from T cells) is a human basic leucine zipper transcription factor that can repress AP-1-mediated transcription. We show here that overexpression of p21(SNFT) in HepG2 cells leads to repression of matrix metalloproteinase-1 by 70-80%. p21(SNFT) interacted with Jun at the matrix metalloproteinase-1 promoter -88 Ets/AP-1 enhancer element, where Jun is known to activate transcription via interaction with Fos and Ets proteins. When p21(SNFT)/Jun dimers bound the element in the presence of Ets, DNA was protected differently than when Fos was paired with Jun. The data suggest a difference in overall conformation between p21(SNFT)-containing and Fos-containing complexes that may be involved in the repression of matrix metalloproteinase-1 by p21(SNFT). Overexpression of p21(SNFT) led to a reduction in invasiveness of HepG2 cells through type I collagen and reconstituted basement membrane, an effect similar to that obtained via direct immunodepletion of matrix metalloproteinase-1. The results indicate that the mechanism of repression of matrix metalloproteinase-1 by p21(SNFT) may be exploited in inhibiting pathological matrix remodeling during cancer progression in vivo.