This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meinhold-Heerlein, I. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Meinhold-Heerlein, I. Articles by Reed, J. C.

(American Journal of Pathology. 2001;158:1335-1344.)
© 2001 American Society for Investigative Pathology

Regular Articles

Expression and Potential Role of Fas-Associated Phosphatase-1 in Ovarian Cancer

Ivo Meinhold-Heerlein^*, Frank Stenner-Liewen^*, Heike Liewen^*, Shinichi Kitada^*, Maryla Krajewska^*, Stanislaw Krajewski^*, Juan M. Zapata^*, Anne Monks, Dominic A. Scudiero, Thomas Bauknecht and John C. Reed^*

From the Program on Apoptosis and Cell Death Research,^*
The Burnham Institute, La Jolla California; the Developmental Therapeutics Program,
Division of Cancer Treatment and Diagnostics, National Cancer Institute, Bethesda Maryland; and the Department of Gynecology and Obstetrics,
University of Bonn, Bonn, Germany

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 0.05) and a low Fas/FAP-1 ratio (P 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.

This article has been cited by other articles:

				M. Krajewska, S. Kitada, J. N. Winter, D. Variakojis, A. Lichtenstein, D. Zhai, M. Cuddy, X. Huang, F. Luciano, C. H. Baker, et al. Bcl-B Expression in Human Epithelial and Nonepithelial Malignancies Clin. Cancer Res., May 15, 2008; 14(10): 3011 - 3021. [Abstract] [Full Text] [PDF]

				W. Zhang, Q. Tong, K. Conrad, J. Wozney, J. Y. Cheung, and B. A. Miller Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1 Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1746 - C1758. [Abstract] [Full Text] [PDF]

				C. N. Landen Jr., C. Lu, L. Y. Han, K. T. Coffman, E. Bruckheimer, J. Halder, L. S. Mangala, W. M. Merritt, Y. G. Lin, C. Gao, et al. Efficacy and Antivascular Effects of EphA2 Reduction With an Agonistic Antibody in Ovarian Cancer. J Natl Cancer Inst, November 1, 2006; 98(21): 1558 - 1570. [Abstract] [Full Text] [PDF]

				S.-H. Yeh, D.-C. Wu, C.-Y. Tsai, T.-J. Kuo, W.-C. Yu, Y.-S. Chang, C.-L. Chen, C.-F. Chang, D.-S. Chen, and P.-J. Chen Genetic Characterization of Fas-Associated Phosphatase-1 as a Putative Tumor Suppressor Gene on Chromosome 4q21.3 in Hepatocellular Carcinoma Clin. Cancer Res., February 15, 2006; 12(4): 1097 - 1108. [Abstract] [Full Text] [PDF]

				V. N. Ivanov, Z. Ronai, and T. K. Hei Opposite Roles of FAP-1 and Dynamin in the Regulation of Fas (CD95) Translocation to the Cell Surface and Susceptibility to Fas Ligand-mediated Apoptosis J. Biol. Chem., January 20, 2006; 281(3): 1840 - 1852. [Abstract] [Full Text] [PDF]

				M. Krajewska, H. Kim, E. Shin, S. Kennedy, M. J. Duffy, Y. F. Wong, D. Marr, J. Mikolajczyk, A. Shabaik, I. Meinhold-Heerlein, et al. Tumor-Associated Alterations in Caspase-14 Expression in Epithelial Malignancies Clin. Cancer Res., August 1, 2005; 11(15): 5462 - 5471. [Abstract] [Full Text] [PDF]

				T. Nedachi and M. Conti Potential role of protein tyrosine phosphatase nonreceptor type 13 in the control of oocyte meiotic maturation Development, October 15, 2004; 131(20): 4987 - 4998. [Abstract] [Full Text] [PDF]

				K. R. Kozak, M. W. Amneus, S. M. Pusey, F. Su, M. N. Luong, S. A. Luong, S. T. Reddy, and R. Farias-Eisner Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: Potential use in diagnosis and prognosis PNAS, October 14, 2003; 100(21): 12343 - 12348. [Abstract] [Full Text] [PDF]

				V. N. Ivanov, P. L. Bergami, G. Maulit, T.-A. Sato, D. Sassoon, and Z.'e. Ronai FAP-1 Association with Fas (Apo-1) Inhibits Fas Expression on the Cell Surface Mol. Cell. Biol., May 15, 2003; 23(10): 3623 - 3635. [Abstract] [Full Text] [PDF]

				H. Gil-Henn and A. Elson Tyrosine Phosphatase-epsilon Activates Src and Supports the Transformed Phenotype of Neu-induced Mammary Tumor Cells J. Biol. Chem., April 25, 2003; 278(18): 15579 - 15586. [Abstract] [Full Text] [PDF]