Departments of Biochemistry, Chonbuk National University Medical School, Jeonju 560-756, Korea
BMB Rep. 2013 Nov;46(11):533-8. doi: 10.5483/bmbrep.2013.46.11.053.
The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy-3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-κB activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.
基质金属蛋白酶（MMPs）的表达与几种人类癌，包括乳腺癌的高转移潜能有关。有几项证据表明，蛋白酪氨酸磷酸酶（PTP）具有促进乳腺癌细胞迁移和转移的功能。我们分析了 PTP 抑制剂是否可以通过 MMP 表达来控制乳腺癌的侵袭。在此，我们研究了新型 PTP 抑制剂 4-羟基-3,3-二甲基-2H 苯并[g]吲哚-2,5(3H)-二酮（BVT948）对 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的 MCF-7 细胞 MMP-9 表达和细胞侵袭的影响。TPA 处理后 MMP-9 的表达和细胞侵袭增加，而 BVT948 预处理则降低了 TPA 诱导的 MMP-9 表达和细胞侵袭。此外，BVT948 抑制了 TPA 处理的 MCF-7 细胞中 NF-κB 的激活。然而，BVT948 并没有阻断 TPA 诱导的 MCF-7 细胞中 AP-1 的激活。我们的结果表明，PTP 抑制剂通过抑制 MMP-9 的表达来阻止乳腺癌的侵袭。
