花生四烯酸代谢相关酶和ERK与乳腺癌转移关系

花生四烯酸代谢相关酶环加氧酶(COX)、脂氧合酶(LOX)和活化的胞外信号调节激酶（p-ERK1/2）等与乳腺癌发生发展具有密切关系.为了进一步阐明它们在乳腺癌转移中的作用及其分子机制，应用反转录PCR（RT-PCR）、免疫印迹和免疫组化等方法，分别检测了乳腺癌细胞系、乳腺癌组织、癌旁组织和转移淋巴结组织中COX-2、5-LOX、12R-LOX、cPLA2和p-ERK1/2的表达水平.结果显示，与对照组相比，在具有高转移潜能的乳腺癌LM MCF-7细胞和MDA-MB-231细胞以及转移淋巴结组织中,COX-2、5-LOX、12R-LOX、cPLA2和p-ERK1/2均有较高水平表达.进而发现，p-ERK1/2的特异性抑制剂PD98059可拮抗LM-MCF-7细胞和MDA-MB-231细胞中COX-2、5-LOX、12R-LOX和cPLA2的高表达.上述结果表明，p-ERK1/2可以通过促进花生四烯酸代谢相关酶的表达促进乳腺癌细胞发生转移.

Relationship Between Enzymes Involved in Arachidonic Acid Metabolism/ERK and Metastasis of Breast Cancer

Many evidences demonstrated that the enzymes involved in arachidonic acid metabolism, such as COX and LOX, and phosphorylated ERK（p-ERK1/2）were closely related to breast cancer. In order to explore the relationship between them，we examined the expression of COX-2、5-LOX、12R-LOX and cPLA2 which were associated with arachidonic acid metabolism by RT-PCR, Western blot analysis and immunohistochemistry in breast cancer cells with different metastatic abilities and clinical tissues of breast cancer, paratumor and metastatic lymph nodes. The results showed that the expression levels of COX-2、5-LOX、12R-LOX、cPLA2 and p-ERK1/2 were higher in breast cancer LM-MCF-7 and MDA-MB-231cells with high metastasis potential and metastatic lymph node tissues, compared with controls. To further reveal the relationship between cPLA2,COX, LOX and p-ERK1/2，we found that PD98059, the specific inhibitor of p-ERK1/2, was effectively able to inhibit the expression of COX-2、5-LOX、12R-LOX and cPLA2 in the breast cancer cells. Thus, our data showed that arachidonic acid metabolism and p-ERK1/2 were closely related to the metastasis of breast cancer cells. p-ERK1/2 was able to promote the arachidonic acid metabolism，which resulted in the metastasis of breast cancer cells.