Use of Cytokines to Prevent Breast Cancer Growth and Progression.
Abstract
This project aims to characterize a novel transcriptional knock out polypeptide (TKO) which we identified in breast cancer cells and which competitively interrupts molecular events in the ISGF3 signaling pathway for interferons-a/Beta (IFNalpha). The TKO action is of clinical significance since IFNs-alpha/Beta are antiproliferative cytokines with significant potential for therapy of stage II or disseminated breast cancer. Improved chromatographic purification of TKO has been achieved during the initial phase of this project and a single polypeptide of ca. 20 kDa associated with ISGF3 DNA-binding inhibition resolved by two dimensional gel electrophoresis. Biochemical sequence analysis and accumulation of purified TKO product for antibody production is progressing. A second objective of this project has been to explore the interaction of the IFN-alpha/Beta signal cascade and the growth stimulatory signal cascade of prolactin (PRL). These molecular cascades can intersect at the level of transductional protein (STAT1, STAT2 of STAT5) phosphorylation. In pilot testing of three cell lines from human breast carcinomas, differences in STAT1 phosphorylation by PRL and IFN-alpha correlated inversely to the level of original tumor differentiation: least effects of PRL and maximum effects of IFN-alpha occurred in a cell line negative for estrogen receptors or other differentiation markers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 31, 1995
- Accession Number
- ADA302228
Entities
People
- Philip M. Grimley
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine