FXYD3 is overexpressed in pancreatic ductal adenocarcinoma and influences pancreatic cancer cell growth

Hany Kayed, Jörg Kleeff, Armin Kolb, Knut Ketterer, Shereen Keleg, Klaus Felix, Thomas Giese, Roland Penzel, Hanswalter Zentgraf, Markus W. Büchler, Murray Korc, Helmut Friess

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The expression and localization of FXYD domain containing ion transport regulator 3 (FXYD3), a transmembrane protein that acts as a chloride channel or chloride channel regulator, was analyzed in pancreatic tissues derived from donors and patients suffering from chronic pancreatitis (CP) or pancreatic ductal adenocarcinoma (PDAC) as well as in pancreatic cancer cells using QRT-PCR, laser-capture microdissection and microarray analysis, in situ hybridization and immunohistochemistry. FXYD3 antisense expressing T3M4 pancreatic cancer cells were generated and compared to control cells using anchorage-dependent and independent growth assays, and xenotransplantation into nude mice. FXYD3 mRNA levels were 3.4-fold increased in PDAC tissues compared to donor specimens (p = 0.006), and 3.9-fold increased in microdissected cancer cells compared to normal pancreatic ductal cells (p = 0.02). FXYD3 was localized in the tubular complexes and PanIN lesions of both CP and PDAC, as well as in pancreatic cancer cells. Downregulation of FXYD3 by stable antisense transfection increased significantly the doubling time of T3M4 pancreatic cancer cells from 44 ± 2 hr to 55 ± 12 hr (p = 0.02). Nude mice transplanted with antisense transfected cells displayed a significant increase in tumor doubling time from 3.3 days ± 1.0 to 4.3 days ± 0.43 (p = 0.058). Anchorage-independent growth and sensitivity to 5-fluorouracil, gemcitabine and cisplatin as well as to MgCl2 were not dependent on the level of FXYD3 expression. In conclusion, overexpression of FXYD3 in pancreatic cancer may contribute to the proliferative activity of this malignancy.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalInternational Journal of Cancer
Volume118
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Chemotherapy
  • Chloride channel
  • Expression profiling
  • Pancreatic cancer
  • TGFβ

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kayed, H., Kleeff, J., Kolb, A., Ketterer, K., Keleg, S., Felix, K., Giese, T., Penzel, R., Zentgraf, H., Büchler, M. W., Korc, M., & Friess, H. (2006). FXYD3 is overexpressed in pancreatic ductal adenocarcinoma and influences pancreatic cancer cell growth. International Journal of Cancer, 118(1), 43-54. https://doi.org/10.1002/ijc.21257