花生四烯酸代谢相关酶和ERK与乳腺癌转移关系

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

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.

Several enzymes associated with arachidonic acid metabolism, such as cyclooxygenase （COX） and lipoxygenase （LOX）, as well as phosphorylated ERK（p-ERK1/2）, are closely related to the development of breast cancer. Reverse transcriptional PCR （RT-PCR）, Western blot analysis and immunohistochemistry were performed to further investigate their roles and the underlined molecular mechanisms in the metastasis of breast cancer. We examined the expression levels of COX-2, 5-LOX, 12R-LOX, cPLA2 and p-ERK1/2 in breast cancer cell lines, as well as tissue samples from breast cancer clinics, including paratumor tissue and metastatic lymph nodes. Our data showed that the COX-2, 5-LOX, 12R-LOX, cPLA2 and p-ERK1/2 were highly expressed in LM-MCF-7 and MDA-MB-231 breast cancer cells, which tends to metastasize to lymph nodes. PD98059, a specific inhibitor of p-ERK1/2 could down-regulated the expressions of COX-2, 5-LOX, 12R-LOX and cPLA2 in both cell lines. The findings suggested that p-ERK1/2 was able to promote the metastasis of breast cancer cells through up-regulating the expression of the enzymes associated with arachidonic acid metabolism.