Accession Number : ADA302228

Title :   Use of Cytokines to Prevent Breast Cancer Growth and Progression.

Descriptive Note : Annual rept. 1 Aug 94-31 Jul 95,

Corporate Author : HENRY M JACKSON FOUNDATION ROCKVILLE MD

Personal Author(s) : Grimley, Philip M.

PDF Url : ADA302228

Report Date : 31 AUG 1995

Pagination or Media Count : 13

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.

Descriptors :   *NEOPLASMS, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, PROPAGATION, PRODUCTION, HUMANS, MOLECULES, TWO DIMENSIONAL, CELLS, BIOCHEMISTRY, PROTEINS, DEOXYRIBONUCLEIC ACIDS, SEQUENCES, PURIFICATION, SIGNALS, THERAPY, ANTIBODIES, MARKERS, PILOT STUDIES, ACCUMULATION, GELS, ELECTROPHORESIS, CANCER, CASCADE STRUCTURES, PHOSPHORYLATION, CHROMATOGRAPHS, PROLACTIN.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE