Taxol and LPS Modulation of c-kit and nm23 Expression in Macrophages and Normal vs. Malignant Breast Cancer Cell Lines.
Abstract
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 and/or 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA357345
Entities
People
- Stephanie N. Vogel
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine