Regular Article
Fas-Signaling and Effects on Receptor Tyrosine Kinase Signal Transduction in Human Breast Epithelial Cells

https://doi.org/10.1006/bbrc.1996.5896Get rights and content

Abstract

Fas-mediated cell death was examined in MCF-10AT preneoplastic human breast epithelial cells. Treatment with anti-Fas for 48 h induced apoptosis with cells exhibiting typical apoptotic features including loss of cell contact, condensation of chromatin, and increased staining of the nuclear membrane. DNA fragmentation occurred in response to anti-Fas treatment. Anti-Fas treatment resulted in decreased p53 protein levels, while bcl-2 and bax protein levels remained unaffected. Cells treated with anti-Fas also exhibited increased tyrosine phosphorylation of the c-met growth factor receptor tyrosine kinase. Immunoprecipitation experiments demonstrated that Fas associated with c-erbB2 and c-met in untreated cells. Treatment with anti-Fas, however, significantly decreased Fas-c-erbB2 and Fas-c-met association. Anti-Fas treatment of these cells caused a significant decrease in p120-GAP levels, ERK-1 levels, and phosphorylation, as well as Grb2-Sos1 and MEK-1-ERK-1 association. These results show that Fas-signaling exerted a suppressive effect on p53 levels and on downstream effectors of receptor tyrosine kinase signal transduction, thereby ensuring cell death.

References (24)

  • L.B. Owen-Schaub et al.

    Cell Immunol.

    (1992)
  • S. Nagata

    Adv. Immunol.

    (1994)
  • Y. Komada et al.

    Blood

    (1995)
  • R. Ni et al.

    Exp. Cell Res.

    (1994)
  • T. Miyashita et al.

    Blood

    (1993)
  • S.J. Korsmeyer

    Immunol. Today

    (1992)
  • E.A. Atkinson et al.

    J. Biol. Chem.

    (1996)
  • N. Oyaizu et al.

    Biochem. Biophys. Res. Commun.

    (1995)
  • K.M. Latinis et al.

    Blood

    (1996)
  • F. McCormick

    Cell

    (1989)
  • K. Chu et al.

    Proc. Natl. Acad. Sci. USA

    (1995)
  • Cited by (25)

    • Hepatocyte growth factor receptor c-MET is associated with FAS and when activated enhances drug-induced apoptosis in pediatric B acute lymphoblastic leukemia with TEL-AML1 translocation

      2007, Journal of Biological Chemistry
      Citation Excerpt :

      CD19+, REH, and 697 cells express FAS (Fig. 2B). c-MET and FAS Co-precipitation— The co-precipitation of c-MET and FAS in breast neoplastic cells and in hepatoblastoma cells was observed, and this suggests that this association might have an effect on the apoptotic activity of FAS (25, 26). So we questioned whether differences in c-MET expression might have a regulatory role in FAS function.

    • Ras GTPase is essential for Fas-mediated activation of phospholipase D in A20 cells

      2000, Biochemical and Biophysical Research Communications
    • Enhanced Fas/CD95-mediated apoptosis by epidermal growth factor in human endometrial epithelial cells

      1999, European Journal of Obstetrics and Gynecology and Reproductive Biology
    View all citing articles on Scopus

    Abbreviations: RTK, receptor tyrosine kinasePTK, protein tyrosine kinase; Sos, son of sevenless; GAP, GTPase activator protein; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-receptor kinase; MEK, MAPK/ERK kinase; PAGE, polyacrylamide gel electrophoresis; SH, src homology;

    1

    Corresponding author. Fax: (313) 577-0082.

    View full text