title: Functional expression of tumor necrosis factor-related apoptosis-inducing ligand in human colonic adenocarcinoma cells.
abstract: TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various transformed cell lines. Therefore, we investigated TRAIL sensitivity, TRAIL-induced nuclear factor-kappaB (NF-kappaB) activation, and expression of TRAIL in human colonic adenocarcinoma cell lines (HT-29, LS180, SK-CO-1). All four TRAIL receptors (TRAIL-R1 through TRAIL-R4) are expressed in these cell lines. TRAIL sensitivity was assessed by assay of cell viability. Cancer cell viabilities were 83 +/- 3.1% (HT-29), 90 +/- 4.3% (LS180), and 88 +/- 6.3% (SK-CO-1) at 24 hours after the addition of 100 ng/ml TRAIL, indicating that these cell lines were relatively resistant to TRAIL. Activation of NF-kappaB was variably influenced by TRAIL administration, with no consistent tendency among the cell lines, indicating that TRAIL-induced NF-kappaB activation might be cell-type dependent. In contrast, TRAIL was expressed in the human colonic adenocarcinoma cell lines by Western blotting and RT-PCR. Increased expression of TRAIL on tumor cells was observed by flow cytometry after cytokine stimulation (IFN-gamma, TNF-alpha) or the addition of chemotherapeutic agents (camptothecin, doxolubicin hydrochloride). TRAIL on HT-29 cells was functional and able to induce apoptosis in Jurkat cells. Jurkat cell viability was increased by the addition of TRAILR1-R4-Fc. In the presence of various cytokines or chemotherapeutic agents, functional TRAIL is expressed on the surface of tumor cells, and this expressed TRAIL might contribute to tumor immune privilege by inducing apoptosis of activated human lymphocytes.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohmori
authors.forename: Takahisa
authors.initials: T
authors.lastname: Sakai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Deguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okano
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002166:Camptothecin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D007371:Interferon-gamma; D002166:Camptothecin