Role of Stat-3 in ER - Breast Tumors

Abstract

The hypothesis to be tested in this application is whether STAT family of transcription factors play a role in the development of ER- negative breast carcinomas. During the past year, we have examined the activation status of two STATs, STAT-3 and STAT-5, known to be associated with the proliferation of normal and cancerous breast cell lines. Our results indicate that in a vast majority of theER- negative breast tumor cell lines, STAT-3 exists in a constitutively activated state and is localized in the nucleus. Normal human cell ines do not exii%bit such aii activat%d stat% ur r'ucl%ar localization of STAT-3. Co-immunoprecipitation studies show that Src kinases immnunoprecipitate along with STAT-3 suggesting a physical association between these two proteins. These results suggest that several of the ER-negative breast carcinomas express constitutively activated Src kinases, which mediate the phosphorylation of STAT-3, which in turn could mediate their proliferative function and oncogenicity. The constitutively activated status of STAT-3, therefore serves as a good diagnostic marker for the detection of ER-negative breast carcinoma development. Since STAT-3 activation appears to play a critical role in the proliferative flinction of ER-negative breast carcinomas, Src-STAT-3 pathway offers an excellent target for the development of cancer therapeutic agents.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2000
Accession Number
ADA392389

Entities

People

  • Premkumer Reddy

Organizations

  • Temple University

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Detection
  • Kinases
  • Neoplasms
  • Phosphorylation
  • Proteins
  • Tissue Extracts
  • Transcription Factors
  • Tumor Cell Line

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.