| Lin HL |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=4.693 ------>paper_class3=2 ------>paper_class2=1 ------>vol=121 ------>confirm_bywho=amel ------>insert_bywho=jpl ------>Jurnal_Rank=21.3 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=2555 ------>medlineContent= ------>unit=G0100 ------>insert_date=20071114 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Int. J. Cancer ------>paper_name=2-Methoxyestradiol attenuates phosphatidylinositol 3-kinase/Akt pathway-mediated metastasis of gastric cancer. ------>confirm_date=20071115 ------>tch_id=093131 ------>pmid=17680560 ------>page1=2547 ------>fullAbstract=The major obstacle for the treatment of gastric cancer is recurrence and metastasis; yet, its molecular mechanism is largely unknown. 2-methoxyestradiol (2-ME), a metabolite of the estradiol-17beta, has recently been demonstrated to have multifactorial effects against tumor proliferation and angiogenesis; how these effects are interrelated and act cooperatively is the key question to be elucidated. Akt activation was shown to promote cancer cell invasiveness, and inhibition of Akt phosphorylation by 2-ME was also noted. We herein investigated the significance of PI3K/Akt activation in gastric cancer metastasis and the anti-metastatic effect of 2-ME through attenuation of Akt activity. Immunohistochemistry of PI3K, phosphorylated Akt (p-Akt) and phosphorylated Erk (p-Erk) was performed in tumors from 56 gastric cancer patients, and a significant correlation between PI3K/p-Akt and tumor stage/prognosis was demonstrated (p < 0.05). An in vitro study of 7 gastric cancer cell lines showed a remarkable correlation between PI3K and p-Akt. PI3K/p-Akt overexpression was associated with invasiveness/migration; in contrast, phosphorylation of Erk was not shown to be correlated with invasiveness. In addition, metastatic gastric cancer clones expressed a higher level of PI3K/p-Akt. The anti-metastatic effect of a low dose of 2-ME and inactivation of Akt was demonstrated. 2-ME also exhibited an ability to inhibit gastric cancer cell proliferation and induce G2/M cell cycle arrest at a higher concentration than that required for inhibition of migration. We conclude that the activation of PI3K/Akt pathway is involved in the late-stage progression and metastasis of gastric cancer, and attenuation of p-Akt by 2-ME suppresses metastasis. ------>tmu_sno=None ------>sno=16171 ------>authors2=Yang MH ------>authors3=Wu CW ------>authors4=Chen PM ------>authors5=Yang YP ------>authors6=Chu YR, Kao CL, Ku HH, Lo JF, Liou JP, Chi CW, Chi ------>authors6_c= ------>authors=Lin HL ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=2-Methoxyestradiol attenuates phosphatidylinositol 3-kinase/Akt pathway-mediated metastasis of gastric cancer. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2007 ------>submit_flag=None ------>publish_month=1 |