Use of Cytokines to Prevent Breast Cancer Growth and Progression.
Abstract
Goals of this project include: (I) characterization of a novel transcriptional knock out (TKO) factor which negatively regulates signal activation t)y type I interferons (!FN-cxJ% in breast cancer cells; and L)2 analysis of signal interactions of IFN-aI% and prolactin (pRL) in breast cancer cells. W Improved purification of ThO from suspension cultures of huanan cancer cells has been achieved: a single fimctionally active polypeptide of -20 kDa has been isolated. Approxiinately 300 ng of ThO is obtained per batch of 7011010 cells, and samples are in process for proteolytic digestion and mass spectrometric analysis. (J2 PRL interactions with IFN-a!% were explored in differentiated (T47D, MCF-7) and undifferentiated (BT-20) cells. !FN%!% predictably activated Jaki and Tyk2 protein tyrosine kinases (pTK) involved in Stat2-Statl phosphorylations. Whereas PRL typically activates Jak2, it also activated Jaki and Tyk2. while differential regulation of pTh activity may be one control mechanism influencing PRL gene transactivation signals; there nevertheless was no evidence of antagonism between IFN-a!% and PRL at the level of Stat2-Statl activation. Indeed, additive Stat activation was found in T47D and MCF-7 cells. While PRL invariably activated Stat 1, activation of Stat3 and Stat5 proved selective. Current work is probing the mechanisms and consequences of such'signal diversity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1996
- Accession Number
- ADA325362
Entities
People
- Phillip M. Grimley
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine