Accession Number : ADA325362

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

Descriptive Note : Annual rept. 1 Aug 95-31 Jul 96,

Corporate Author : HENRY M JACKSON FOUNDATION ROCKVILLE MD

Personal Author(s) : Grimley, Phillip M.

PDF Url : ADA325362

Report Date : AUG 1996

Pagination or Media Count : 18

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.

Descriptors :   *MILITARY MEDICINE, *CELLS(BIOLOGY), *CULTURES(BIOLOGY), *PREVENTIVE MEDICINE, *GROWTH(PHYSIOLOGY), *BREAST CANCER, CONTROL, ACTIVATION, CONTROL SYSTEMS, INTERACTIONS, PURIFICATION, SIGNALS, INTERFERON, MASS SPECTROMETRY, PROLACTIN.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE