Taxol and LPS Modulation of c-kit and nm23 Expression in Macrophages and Normal vs. Malignant Breast Cancer Cell Lines.
Annual rept. 24 Jun 97-23 Jun 98
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 lipopolysaccharide LPS the capacity to elicit microtubule-independent, intracellular signaling in murine macrophages that activate kinase cascades that lead 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, metatstatic breast cancer. In addition, modulation of adrenomedulin AM, as well as a panel of inflammatory genes, were examined in murine macrophages andor breast cancer cells stimulated by LPS or Taxol. Using optimized conditions for the detection of mRNA species by reverse transcriptase polymerase chain reaction RT-PCR, we have 1 nearly completed studies on the modulation of AM in macrophages, 2 demonstrated differential modulation of nm23 and c-kit mRNA in the murine breast cancer cell line, DA-3, and 3 demonstrated that both LPS and Taxol strongly up-regulate expression of a panel pro-inflammatory genes in the breast cancer cell line. We have been granted a no-cost extension to move forward with our analysis of other murine and human breast cancer cell lines as originally proposed.
- Medicine and Medical Research