Fas and Fas-ligand expression in human pancreatic cancer

Marko Kornmann, Toshiyuki Ishiwata, Jörg Kleeff, Hans G. Beger, Murray Korc

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Objective: To investigate Fas and FasL expression in pancreatic tissues and cultured pancreatic cancer cell lines, and to assess the ability of anti- Fas antibodies to induce apoptosis. Summary Background Data: Activation of the Fas receptor by Fas-ligand (FasL) results in apoptosis, and dysregulation of this pathway may contribute to abnormal cell proliferation. Methods: Northern blotting and immunohistochemistry were used to compare Fas and FasL expression in normal and cancerous tissues. DNA 3'-OH end labeling was used to detect apoptotic cells. The effects of Fas activation on cell growth and signaling pathways were investigated in culture. Results: Pancreatic cancers exhibited increased Fas RNA levels, whereas FasL mRNA levels were similar in both groups. De- spite the colocalization of Fas and FasL in the cancer cells, an apoptotic signal was present in approximately 10% of these cells in only 2 of 16 cancer samples. Fas and FasL were coexpressed in all four cell lines, whereas Fas-associated phosphatase 1 was below the level of detection in all cell lines. Only COLO-357 cells underwent apoptosis after Fas activation. Apoptosis was associated with enhanced activation of jun kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). In the presence of actinomycin D, Fas antibody also induced apoptosis in the other three cell lines. Conclusions: These results suggest that pancreatic cancer cells are resistant to Fas-mediated apoptosis by mechanisms excluding receptor downregulation or Fas-associated phosphatase upregulation and raise the possibility that Fas-mediated apoptosis may be dependent on the activation of the JNK/p38 MAPK pathway in these cells.

Original languageEnglish (US)
Pages (from-to)368-379
Number of pages12
JournalAnnals of Surgery
Volume231
Issue number3
DOIs
StatePublished - Mar 2000
Externally publishedYes

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Fas Ligand Protein
Pancreatic Neoplasms
Apoptosis
Cell Line
p38 Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Phosphotransferases
CD95 Antigens
Dactinomycin
Northern Blotting
Anti-Idiotypic Antibodies
Neoplasms
Up-Regulation
Down-Regulation
Immunohistochemistry
Cell Proliferation
RNA
Messenger RNA
Antibodies
DNA

ASJC Scopus subject areas

  • Surgery

Cite this

Kornmann, M., Ishiwata, T., Kleeff, J., Beger, H. G., & Korc, M. (2000). Fas and Fas-ligand expression in human pancreatic cancer. Annals of Surgery, 231(3), 368-379. https://doi.org/10.1097/00000658-200003000-00010

Fas and Fas-ligand expression in human pancreatic cancer. / Kornmann, Marko; Ishiwata, Toshiyuki; Kleeff, Jörg; Beger, Hans G.; Korc, Murray.

In: Annals of Surgery, Vol. 231, No. 3, 03.2000, p. 368-379.

Research output: Contribution to journalArticle

Kornmann, M, Ishiwata, T, Kleeff, J, Beger, HG & Korc, M 2000, 'Fas and Fas-ligand expression in human pancreatic cancer', Annals of Surgery, vol. 231, no. 3, pp. 368-379. https://doi.org/10.1097/00000658-200003000-00010
Kornmann M, Ishiwata T, Kleeff J, Beger HG, Korc M. Fas and Fas-ligand expression in human pancreatic cancer. Annals of Surgery. 2000 Mar;231(3):368-379. https://doi.org/10.1097/00000658-200003000-00010
Kornmann, Marko ; Ishiwata, Toshiyuki ; Kleeff, Jörg ; Beger, Hans G. ; Korc, Murray. / Fas and Fas-ligand expression in human pancreatic cancer. In: Annals of Surgery. 2000 ; Vol. 231, No. 3. pp. 368-379.
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