The Role of ROS in Breast Cancer Metastasis
Abstract
Cancer cells can generate constitutively reactive oxygen species (ROS), which are thought to promote cell proliferation, cell motility, invasion and angiogenesis, all of them prerequisites for tumor metastasis. Recently novel ROS-generating enzymes termed Nox have been identified in epithelial cells, Transfer of Nox into non-transformed fibroblasts increased ROS production and rendered these cells tumorigenic. The goal of our project was to identify Nox family members in cancer cells and to evaluate their regulation and cellular function. Breast cancer cell lines were screened by RT-PCR for the presence of various nox and neutrophil NADPH oxidase genes and contained Nox3, Nox4, Nox5 as well as p22(phox) and p67(phox). Reactive oxygen production by Nox4 is dependent on the oxidase component p22(phox), growth factors and cellular adhesion. We observed down-regulation of ROS production when attachment of cells was abolished or under serum withdrawal. In terms of function, Nox4-stimulated ROS generation led to up-regulation of VEGF, a promoter of angiogenesis. The activity of deregulated Nox proteins in cancer cells may have wide ranging implications in tumorigenic events including metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA416744
Entities
People
- Ulla G. Knaus
Organizations
- Scripps Research