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 leading 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. Modulation of adrenomedulin (AM), as well as a panel of inflammatory genes, were also examined in murine macrophages and/or breast cancer cells stimulated by LPS or Taxol. Using optimized conditions for detection of mRNA species by reverse transcriptase polymerase chain reaction (RT-PCR): (1) we completed studies on the modulation of AM in macrophages, (2) demonstrated differential modulation of NM-23 and c-kit mRNA in the murine breast cancer cell line, DA-3, and (3) demonstrated that LPS and/or Taxol strongly up-regulate expression of a panel pro-inflammatory genes in a murine (DA-3) and a human (MDA-MB-231) breast cancer cell lines. (4) Lastly, in the presence of DA-3 tumor cells, stimulation of macrophages by LPS or Taxol plus IPN-gamma results is a significant increase in the capacity of the macrophages to release nitric oxide (NO), shown previously to be tumoricidal. In toto, these studies largely complete and exceed the proposed scope of the research outlined in our original proposal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA377166
Entities
People
- Stefanie N. Vogel
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine