Taxol and LPS Modulation of c-kit and nm23 Expression in Macrophages and Normal vs. Malignanat Breast Cancer Cell Lines.
Annual rept. 24 Jun 96-23 Jun 97,
HENRY M JACKSON FOUNDATION ROCKVILLE MD
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Taxol is a microtubule poison that has been used successfully in refractory breast cancer. Apart from its well characterized anti-mitotic effects, Taxol shares with bacterial lipopoly- saccharide LPS the capacity to elicit microtubule-independent, intracellular signaling pathways in murine macrophages that activate a serinethreonine and tyrosine kinase cascade that leads to expression of many genes. This IDEA grant proposed to test the ability of Taxol to up-regulate expression of two genes, nm23 and c-kit, whose expression is down-regulated in advanced, metastatic breast cancer. In addition, modulation of adrenomedulin AM, a gene expressed by both cancer cells and macrophages, has been examined. To date, we have 1 optimized conditions for the detection of nm23, c-kit, and AM mRNA by reverse transcriptase polymerase chain reaction RT-PCR in murine cells, 2 demonstrated differential expression of rnn23 mRNA in two melanoma cell lines TK1735 2-4 and the nm23 transfectant, TK1735 4- 6, and 3 demonstrated that both LPS and Taxol strongly up-regulate expression of AM, and to a lesser extent, c-kit and nm23, in LPS-responsive murine macrophages. We are now ready to move forward with our analysis of breast cancer cell lines as originally proposed.
- Medicine and Medical Research
- Anatomy and Physiology