The Role of Capase-8 in Breast Carcinoma Cells

Abstract

CD95 mediated apoptosis is important for numerous processes, and often tumor cells develop a resistance to CD95 mediated apoptosis. NCF7-Fas-Bcl-xl cells, which are a model of a breast carcinoma cell, are protected from CD95 mediated apoptosis by binding and inactivating active caspase-8 generated at the DISC on mitochondria. The mechanism of this binding and its functional relevance is the subject of the study. The binding properties and mechanism of the subsequent degradation is addressed. Additionally, CD95 signaling in these apoptosis resistant tumor cells was determined to activate numerous signaling pathways, resulting in the activation of multiple genes including anti-apoptotic, pro- proliferative, and pro-tumorigenic genes, and ultimately an increase in motility and invasiveness. This increase was determined to be dependent on the activation of the NF-KB pathway, as well as the Erkl/2 pathway, and interestingly, caspase-8 activity. These observations are profound and relevant to the study of numerous breast cancers, and my redefine the way in which CD95 signaling is viewed. It also addresses the role of caspase-8 in breast carcinoma cells, which may induce tumor progression in certain circumstances rather than the death of the cell.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2004
Accession Number
ADA424040

Entities

People

  • Bryan C. Barnhart
  • Marcus E. Peter

Organizations

  • University of Chicago

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biological Factors
  • Blood
  • Breast Cancer
  • Cancer
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Lymphocytes
  • Neoplasms
  • Proteins
  • T Lymphocytes
  • Transcription Factors
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology