Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer

Am J Pathol. 2001 Apr;158(4):1335-44. doi: 10.1016/S0002-9440(10)64084-9.

Abstract

Fas-associated phosphatase-1 (FAP-1) is a protein-tyrosine phosphatase that binds the cytosolic tail of Fas (Apo1, CD95), presumably regulating Fas-induced apoptosis. Elevations of FAP-1 protein levels in some tumor cell lines have been correlated with resistance to Fas-induced apoptosis. To explore the expression of FAP-1 in ovarian cancer cell lines and archival tumor specimens, mouse monoclonal and rabbit polyclonal antibodies were generated against a FAP-1 peptide and recombinant FAP-1 protein. These antibodies were used for immunoblotting, immunohistochemistry, and flow-cytometry analysis of FAP-1 expression in the Fas-sensitive ovarian cancer lines HEY and BG-1, and in the Fas-resistant lines OVCAR-3 FR and SK-OV-3. All methods demonstrated high levels of FAP-1 in the resistant lines OVCAR-3 FR and SK-OV-3, but not in the Fas-sensitive lines HEY and BG-1. Furthermore, levels of FAP-1 protein also correlated with the amounts of FAP-1 mRNA, as determined by reverse transcriptase-polymerase chain reaction analysis. FAP-1 protein levels were investigated by immunoblotting in the National Cancer Institute's panel of 60 human tumor cell lines. Although FAP-1 failed to correlate with Fas-resistance across the entire tumor panel, Fas-resistance correlated significantly with FAP-1 expression (P: < or = 0.05) and a low Fas/FAP-1 ratio (P: < or = 0.028) in ovarian cancer cell lines. FAP-1 expression was also evaluated in 95 archival ovarian cancer specimens using tissue-microarray technology. FAP-1 was expressed in nearly all tumors, regardless of histological type or grade, stage, patient age, response to chemotherapy, or patient survival. We conclude that FAP-1 correlates significantly with Fas resistance in ovarian cancer cell lines and is commonly expressed in ovarian cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biopsy
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Drug Resistance
  • Female
  • Humans
  • Jurkat Cells
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology
  • Ovary / metabolism
  • Ovary / pathology
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13
  • Protein Tyrosine Phosphatases / metabolism
  • Protein Tyrosine Phosphatases / physiology*
  • Tumor Cells, Cultured
  • fas Receptor / physiology

Substances

  • Carrier Proteins
  • fas Receptor
  • Protein Phosphatase 1
  • PTPN13 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 13
  • Protein Tyrosine Phosphatases
  • Ptpn13 protein, mouse