Matrix metalloproteinase expression in breast cancer
Matrix metalloproteinase expression in breast cancer
复制标题
DOI：
10.1016/s0022-4804(03)00007-6
复制
发表时间：
2003-04-01
影响因子：
2.2
通讯作者：
Appert, HE
中科院分区：
文献类型：
--
作者：
Bartsch, JE;Staren, ED;Appert, HE
背景资料。基质金属蛋白酶(MMPs)被认为是某些肿瘤侵袭和转移的可能介质。我们的目标是调查哪些MMPs在乳腺肿瘤细胞中有结构性表达，哪些可以被一些已知影响其他细胞系统中MMPs表达的药物上调。我们用半定量RT-PCR和明胶酶谱检测了MMP1-16在乳腺癌细胞株MDA-MB-231、T47D和MCF-7中的表达。用12-O-十四酰基酚-3-乙酸酯(TPA)、刀豆蛋白-A(ConA)、纤维连接蛋白模拟肽GRGDSP(RGD)、细胞外基质(ECM)成分和抗整合素抗体检测基质金属蛋白酶的可能上调。应用丝裂原活化蛋白激酶抑制物(MAPK-I)研究细胞内信号转导途径及对基质金属蛋白酶表达的调控。AMP 1、2、7-11、13、14和16在某些肿瘤细胞系中呈结构性表达，而在正常乳腺上皮细胞中不表达。给予TPA、Con-A和RGD后，AMP 1、2、9和10的表达增加。经ECM组分或抗整合素抗体处理后，MDA-MB-231或MCF-7中AMP的表达均未见上调。MAPK-I对MDA-MB-231和MCF-7细胞的组成性基质金属蛋白酶表达无影响，但可降低或取消TPA上调基质金属蛋白酶-9的作用。乳腺肿瘤细胞系结构性地表达大量的MMPs。由于Con-A、纤维连接蛋白模拟肽RGD和TPA可上调基质金属蛋白酶的表达，而MAPK拮抗剂对其有抑制作用，因此MAPK信号似乎在这一表达中发挥了作用。(C)2003年埃尔塞维尔科学公司(美国)。
Background. Matrix metalloproteinases (MMPs) have been implicated as possible mediators of invasion and metastasis in some cancers. Our objective was to investigate which MMPs were constitutively expressed in breast tumor cells versus those that could be up-regulated by a number of agents known to affect MMP expression in other cell systems.Methods. We evaluated expression of MMPs 1-16 in breast tumor cell lines MDA-MB-231, T47D, and MCF-7 using semiquantitative RT-PCR and gelatin zymography. Exposure to 12-O-tetradecanoylphorbal-3-acetate (TPA), concanavalin-A (Con-A), the fibronectin-mimetic peptide GRGDSP (RGD), extracellular matrix (ECM) components, and anti-integrin antibodies was used to test for possible MMP up-regulation. Mitogen-activated protein kinase inhibitors (MAPK-I) were used to evaluate signal transduction pathways and regulation of MMP expression.Results. AMPS 1, 2, 7-11, 13, 14, and 16 were constitutively expressed in some tumor cell lines but not in normal breast epithelial cells. Administration of TPA, Con-A, and RGD increased the expression of AMPS 1, 2, 9, and 10. No AMP up-regulation was seen in MDA-MB-231 or MCF-7 after exposure to ECM components or after exposure to anti-integrin antibodies. MAPK-I had no effect on constitutive MMP expression but reduced or abolished the TPA up-regulation of MMP-9 in MDA-MB-231 and MCF-7.Conclusions. Breast tumor cell lines constitutively express a number of MMPs. Because MMP expression can be up-regulated by Con-A, the fibronectin-mimetic peptide RGD, and TPA while being susceptible to inhibition by MAPK antagonists, MAPK signaling appears to play a role in this expression. (C) 2003 Elsevier Science (USA).