Functional expression of TWEAK in human colonic adenocarcinoma cells.

Abstract

The TNF-like weak inducer of apoptosis (TWEAK) can induce diverse cellular responses, including cell death, inflammation, migration, and proliferation in various transformed cell lines. We investigated TWEAK sensitivity, TWEAK effects on nuclear factor-kappaB activation, and expression of TWEAK in the HT-29, LS180, SK-CO-1 and SW480 human colonic adenocarcinoma cell lines, all of which express the TWEAK receptor (Fn14). TWEAK alone induced cell death in SW480 cells and induced cell death of HT-29 cells after addition of IFN-gamma, actinomycin D or cycloheximide. TWEAK did not affect cell viability of LS-180 or SK-CO-1 cells. Activation of NF-kappaB was not obviously influenced by TWEAK in any of the cell lines. All four human colonic adenocarcinoma cell lines constitutively expressed TWEAK mRNA, protein and membrane-bound TWEAK antigen, as detected by RT-PCR, Western blotting and flow cytometry. Stimulation by an anticancer drug (camptothecin) augmented cell surface expression of TWEAK and all human colonic adenocarcinoma tissue samples studied (n=59) demonstrated positive staining for TWEAK antigen. Soluble TWEAK was detected in culture medium of these cell lines by ELISA and conditioned medium from SW480 cells incubated with anti-TWEAK antibody significantly inhibited endothelial cell tube formation in Matrigels. Thus, functional expression of TWEAK from human colonic adenocarcinoma cells may contribute to neovascularization.

• Authors: Tomoyuki Kawakita, Katsuya Shiraki, Yutaka Yamanaka, Yumi Yamaguchi, Yukiko Saitou, Naoyuki Enokimura, Norihiko Yamamoto, Hiroshi Okano, Kazushi Sugimoto, Kazumoto Murata, Takeshi Nakano
• Journal: International journal of oncology (Int J Oncol) Vol. 26 Issue 1 Pg. 87-93 (Jan 2005) ISSN: 1019-6439 [Print] Greece
• PMID: 15586228 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Apoptosis Regulatory Proteins
• Carrier Proteins
• Culture Media, Conditioned
• Cytokine TWEAK
• NF-kappa B
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• TNFRSF12A protein, human
• TNFSF12 protein, human
• TWEAK Receptor
• Tumor Necrosis Factors
• Luciferases
• Camptothecin

Topics

• Adenocarcinoma (immunology, metabolism)
• Antibodies (pharmacology)
• Apoptosis Regulatory Proteins
• Camptothecin (pharmacology)
• Carrier Proteins (analysis, genetics, metabolism)
• Cell Membrane (immunology, metabolism)
• Colonic Neoplasms (immunology, metabolism)
• Culture Media, Conditioned
• Cytokine TWEAK
• Endothelial Cells (drug effects)
• Genes, Reporter (genetics)
• Humans
• Luciferases (analysis, genetics)
• NF-kappa B (genetics, metabolism)
• Neovascularization, Pathologic (metabolism, physiopathology)
• RNA, Messenger (analysis, metabolism)
• Receptors, Tumor Necrosis Factor (metabolism)
• TWEAK Receptor
• Tumor Necrosis Factors