Novel Angiogenic Domains: Use in Identifying Unique Transforming and Tumor Promoting Pathways in Human Breast Cancer
Abstract
Breast cancers in humans often grow slowly or even remain undetectable for long periods of time only to reappear in discreet stages as progressively more malignant tumors. Recently, studies in both human cancers and experimental cancers in animals have established that cancers become progressively more aggressive in incremental steps that result form genetic mutations or "switches" in the tumor cells themselves. We have found that the two growth/differentiation promoting cytokines pleiotrophin (PTN) and midkine (MK) act as "switches" when introduced into breast cancer cells to stimulate more aggressive growth and induce new intratumor blood vessel formation, ie, an "angiogenic switch." Different studies have found constitutive expression of either the PTN or MK genes in over 50% of human breast cancers, suggesting our data is very important and relevant to human breast cancer. We now plan to pursue the mechanism of PTN signaling in both MMTV driven pleiotrophin%gain of function mice and "knock-out" pleiotrophin mice developed in the laboratory and the mechanisms of downstream PTN signaling with different "chip technology-driven strategies available to us in the laboratory.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA425651
Entities
People
- Thomas F. Deuel
Organizations
- Scripps Research