期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 174, 期 1, 页码 265-275出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.071006
关键词
-
类别
资金
- NATIONAL CANCER INSTITUTE [Z01BC010566, ZIABC010566, Z01SC000165, ZIASC000165] Funding Source: NIH RePORTER
A well-characterized murine osteosarcoma model for metastasis and invasion was used in this study to determine the role of AP-1 in the progression of this disease. We analyzed K12 and K7M2 cells, two clonally related murine osteosarcoma cell lines that have been characterized as low metastatic or high metastatic, respectively, for AP-1 components and activity. AP-1 DNA binding was similar between the two cell fines; however AP-1 transcriptional activity was enhanced by 3- to 5-fold in K7M2 cells relative to that in K12 cells. The AP-1 complexes in K12 and K7M2 cells was composed primarily of cJun, JunD, FosB, Fra1, and Fra2, with the contribution of individual components in the complex varying between the two cell lines. In addition, an increase in phosphorylated cJun, JNK activity, and phosphorylated ERK1/2 was associated with the more metastatic osteosarcoma phenotype. The significance of AP-1 activation was confirmed by conditional expression of TAM67, a dominant negative mutant of cJun. Under conditions where TAM67 inhibited AP-1 activity in K7M2 cells, migration and invasion potential was significantly blocked. Tam67 expression in aggressive osteosarcoma cells decreased long-term in vivo experimental metastasis and increased survival of mice. This study shows that differences in metastatic activity can be due to AP-1 activation. The inhibition of AP-1 activity may serve as a therapeutic tool in the management of osteosarcoma. (Am J Pathol 2009, 174:265-275; DOI: 10.2353/ajpath.2009.071006)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据