Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer.
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.
Meinhold-Heerlein
I
I
Program on Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, CA 92037, USA.
Stenner-Liewen
F
F
Liewen
H
H
Kitada
S
S
Krajewska
M
M
Krajewski
S
S
Zapata
J M
JM
Monks
A
A
Scudiero
D A
DA
Bauknecht
T
T
Reed
J C
JC
D001706:Biopsy; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology
D002352:Carrier Proteins; D019014:fas Receptor; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; C516743:Ptpn13 protein, mouse