Differential expression and regulation of cyclooxygenase-1 and -2 in two human breast cancer cell lines.
Differential expression and regulation of cyclooxygenase-1 and -2 in two human breast cancer cell lines.
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发表时间：
1996-11
期刊：
影响因子：
11.2
通讯作者：
Xin-hua Liu;D. Rose
中科院分区：
文献类型：
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作者：
Xin-hua Liu;D. Rose
环氧合酶（考克斯），也称为前列腺素内过氧化物合酶，是花生四烯酸代谢转化为花生四烯酸（PGs）和相关类花生酸的限速酶。一些人类乳腺癌合成大量的PGE 2，但涉及的调节机制尚不清楚。我们研究了这种酶的两种亚型考克斯-1和考克斯-2的表达，十四烷酰佛波醇乙酸酯（TPA）对它们的调节，以及两种具有不同生物学表型的人乳腺癌细胞系中相关的PGE 2产生。雌激素依赖性MCF-7细胞表现出相对较高的考克斯-1表达;考克斯-2几乎检测不到，但TPA（10 nM）处理可短暂诱导表达。相反，雌激素非依赖性、高侵袭性、转移性MDA-MB-231细胞系显示考克斯-1的低表达，但考克斯-2的组成性水平高。这种高考克斯-2表达适用于蛋白质和mRNA，并且在TPA存在下在相对长的时间内进一步增加。两种细胞系产生PGE 2的程度与考克斯-2蛋白的水平密切相关，这表明该同种型是其组成性和促分裂原诱导的PGE 2合成所必需的。此外，考克斯-2的过度表达和持续表达可能受到乳腺肿瘤激素状态的影响，并且似乎是侵袭性、转移性表型的特征。
Cyclooxygenase (COX), also referred to as prostaglandin endoperoxide synthase, is the rate-limiting enzyme for the metabolic conversion of arachidonic acid to prostaglandins (PGs) and related eicosanoids. Some human breast cancers synthesize large quantities of PGE2, but the regulatory mechanisms involved are unclear. We have examined the expression of the two isoforms of this enzyme, COX-1 and COX-2, their regulation by tetradecanoyl phorbol acetate (TPA), and the associated PGE2 production in two human breast cancer cell lines with different biological phenotypes. Estrogen-dependent MCF-7 cells exhibited a relatively high expression of COX-1; COX-2 was barely detectable but was transiently induced by treatment with TPA (10 nM). In contrast, the estrogen-independent, highly invasive, metastatic MDA-MB-231 cell line showed a low expression of COX-1 but a high constitutive level of COX-2. This high COX-2 expression applied to both the protein and mRNA and increased further over a relatively long period of time in the presence of TPA. The extent of PGE2 production by the two cell lines correlated well with the level of COX-2 protein, suggesting that this isoform is required for both their constitutive and mitogen-induced PGE2 synthesis. Moreover, overexpression and persistent expression of COX-2 may be influenced by breast tumor hormone status and seem to be a feature of the aggressive, metastatic phenotype.