The Role of MKK4 in the Metastatic Colonization of Ovarian Cancer
Abstract
Mitogen activated protein kinase kinase 4 (MKK4) a member of the stress activated protein kinase signaling pathway acts as a metastasis suppressor protein in ovarian cancer. Introduction of MKK4 into a highly metastatic human ovarian cancer cell line reduces the number of overt metastases by 90% and prolongs animal survival by 70%. Our specific aims in this proposal included determining the mechanism by which MKK4 mediated metastasis suppression and determining whether introduction of MKK4 a potent activator of the JNK pathway in conjunction with chemotherapeutic agents known to activate JNK would potentiate MKK4s effects on survival and JNK activation. Our key findings during the period of the proposal included the following: 1) MKK4 mediates metastasis suppression via the p38 pathway 2) MKK4 does not mediate metastasis suppression via the JNK pathway 3) MKK4 kinase activity is required for MKK4 induced metastasis suppression. In the past year our findings have included 4) MKK4 expression does not augment the effects of either cisplatin or paclitaxel on metastases in vivo. 5) There do not appear to be any differences in JNK or p38 activation levels in metastases taken from mice injected with MKK4 and treated with chemotherapy (cisplatin or paclitaxel) over chemotherapy alone.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2006
- Accession Number
- ADA462588
Entities
People
- S. D. Yamada
Organizations
- University of Chicago