Munir I, Fukunaga K, Kanasaki H, Miyazaki K, Ohba T, Okamura H, Miyamoto E
Department of Pharmacology, Kumamoto University Schoolof Medicine, Kumamoto 860-0811, Japan.
Biol Reprod. 2000 Sep;63(3):933-41. doi: 10.1095/biolreprod63.3.933.
The regulation of expression of cyclooxygenase 2 (COX-2) was investigated by treatment with PGE(2) in human endometrial adenocarcinoma cell line HEC-1B. One microM PGE(2) could stimulate the expression of COX-2 approximately twofold in this cell line. The same concentration of PGE(2) also stimulated activation of mitogen-activated protein kinase (MAP kinase) and protein kinase B (PKB). PGE(2)-induced MAP kinase activation was sensitive to a MAP kinase kinase (MEK) inhibitor, PD098059, and a protein kinase A inhibitor, H-89. PD098059 and H-89 also partially inhibited the expression of COX-2 stimulated by PGE(2). PGE(2) could stimulate the activation of PKB, which was sensitive to phosphatidylinositol-3-OH kinase (PI3K) inhibitor, wortmannin. Whereas wortmannin alone partially inhibited the expression of COX-2, a combination of wortmannin and PD098059 totally inhibited PGE(2)-mediated COX-2 expression. These results suggest that MAP kinase and PI3K pathways are stimulated with PGE(2), and that both of these pathways are involved in the expression of COX-2. In addition, they also suggest that protein kinase A remains upstream of PGE(2)-induced activation of MAP kinase in HEC-1B cells.
通过用前列腺素E2（PGE2）处理人子宫内膜腺癌细胞系HEC-1B，研究了环氧化酶2（COX-2）表达的调控。1微摩尔的PGE2可使该细胞系中COX-2的表达增加约两倍。相同浓度的PGE2还可刺激丝裂原活化蛋白激酶（MAP激酶）和蛋白激酶B（PKB）的激活。PGE2诱导的MAP激酶激活对MAP激酶激酶（MEK）抑制剂PD098059和蛋白激酶A抑制剂H-89敏感。PD098059和H-89也部分抑制了PGE2刺激的COX-2表达。PGE2可刺激PKB的激活，PKB的激活对磷脂酰肌醇-3-OH激酶（PI3K）抑制剂渥曼青霉素敏感。虽然单独使用渥曼青霉素可部分抑制COX-2的表达，但渥曼青霉素和PD098059联合使用可完全抑制PGE2介导的COX-2表达。这些结果表明，PGE2可刺激MAP激酶和PI3K途径，且这两条途径均参与COX-2的表达。此外，这些结果还表明，蛋白激酶A在HEC-1B细胞中位于PGE2诱导的MAP激酶激活的上游。
