Function of FasL Reverse Signaling in Survival and Growth of Breast Cancer Cells

Abstract

We have investigated a possible role of Fas ligand (FasL) in reverse signaling to mediate cell survival and growth signals through its intracellular proline-rich domain to protect FasL-expressing breast cancer cells from cell death. We have generated expressing constructs containing either a wild-type or the cytoplasmic proline-rich domain-deletion mutant cDNAs of FasL and transfected them into NIH 3T3 cells. We found that the cells expressing the wild-type FasL are more resistant to Fas-induced cell death than the mutant, suggesting that the cytoplasmic proline-rich domain of FasL indeed promote cell survival. We also generated bacteria-expressed GST-FasL fusion proteins and used these proteins to identify proteins that physically interact with the cytoplasmic domain of FasL. Two protein bands from 35S-Methioline-labled 3T3 cell lysates were found to specifically bind to FasL. We are currently characterizing these proteins. These results suggest a novel function of FasL in promoting survival and growth of breast cancer cells. The complete understanding of function and mechanism of FasL in tumor cells is necessary for developing effective diagnostic and therapeutic reagents to treat breast cancer patients.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2002
Accession Number
ADA410807

Entities

People

  • Qiang Yu

Organizations

  • Boston University

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Culture Techniques
  • Diseases And Disorders
  • Lymphocytes
  • Molecules
  • Neoplasms
  • Proteins
  • Survival
  • T Lymphocytes

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Prostate Cancer Biology.