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RETRACTED ARTICLE: EphA2: a determinant of malignant cellular behavior and a potential therapeutic target in pancreatic adenocarcinoma

Oncogene volume 23, pages 1448–1456 (2004)Cite this article

This article was retracted on 09 February 2023

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Abstract

The EphA2 receptor tyrosine kinase is overexpressed in a variety of human cancers. We sought to characterize the role of EphA2 in pancreatic adenocarcinoma and, using RNA interference (RNAi) mediated by small interfering RNA (siRNA), we determined the effects of suppressing EphA2 expression in vitro and in vivo. EphA2 expression in PANC1, MIAPaCa2, BxPC3 and Capan2 cells was assessed by Northern and Western blot. We artificially overexpressed EphA2 by transient transfection and suppressed EphA2 expression using RNAi. Cellular invasiveness was quantified by modified Boyden chamber assay. Anoikis was induced by anchorage-independent polyHEMA culture and caspase 3 activity was quantified fluorometrically. Focal adhesion kinase (FAK) phosphorylation was assessed by immunoprecipitation. EphA2 siRNA treatment was assessed in a nude mouse xenograft model. Pancreatic adenocarcinoma cells differentially express EphA2. Inherent and induced EphA2 overexpression is associated with increased cellular invasiveness and anoikis resistance. EphA2 siRNA suppresses EphA2 expression, cellular invasiveness, anoikis resistance and FAK phosphorylation in vitro and retards tumor growth and inhibits metastasis in vivo. EphA2 is both a determinant of malignant cellular behavior and a potential therapeutic target in pancreatic adenocarcinoma.

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Acknowledgements

The authors gratefully acknowledge the technical assistance of Jan Rounds.

This work was supported by The National Pancreas Foundation and Departmental funds from the Department of Surgery, Brigham and Women's Hospital.

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Authors and Affiliations

  1. Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, 02115, MA, USA

    Mark S Duxbury, Hiromichi Ito, Michael J Zinner, Stanley W Ashley & Edward E Whang

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  1. Mark S Duxbury
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  2. Hiromichi Ito
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  3. Michael J Zinner
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  4. Stanley W Ashley
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  5. Edward E Whang
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Correspondence to Edward E Whang.

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Duxbury, M., Ito, H., Zinner, M. et al. RETRACTED ARTICLE: EphA2: a determinant of malignant cellular behavior and a potential therapeutic target in pancreatic adenocarcinoma. Oncogene 23, 1448–1456 (2004). https://doi.org/10.1038/sj.onc.1207247

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