The Role of MEKK3 Signaling of Pathway in the Resistance of Breast Cancer Cells to TNF-(Alpha)-Mediated Apoptosis
Annual summary rept. 1 May 2003-30 Apr 2004
M D ANDERSON CANCER CENTER HOUSTON TX
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In the past year, we continued to test the hypothesis that NF-kB activation in breast cancer cells plays a critical role in cancer cells resistance to anti-cancer drugs and to TNFalpha treatment, and MEKK3 is an essential component of this process. We finished construction of dominant negative forms of MEKK3 expression vectors and tested the vectors in 293T cells and in breast cancer cell line MCF7. We also prepared two lentiviral vectors for MEKK3 siRNA. The second line of this study is to further determine the regulation of NF-kB and AP-1 activation through MEKK3. Because both the NF-kB and AP-1 pathways are crucial in regulating cell apoptosis, the balance of their activation will determine the outcome of cell survival or apoptosis. We found that MEKK3 is crucial for NF-kB, JNK, and p38 but not for ERK MAPK activation. Furthermore we generated and characterized a unique antibody that recognize active MEKK3. This antibody will allow us to measure the effect of inhibitors andor modulators of MEKK3 activity in breast cancer cells for investigation of the cancer cell sensitive to TNFalpha.
- Medicine and Medical Research