Apoptosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-gamma through caspase 3 and caspase 8.

Adachi, Yasushi; Taketani, Shigeru; Oyaizu, Haruki; Ikebukuro, Kazuya; Tokunaga, Rikio; Ikehara, Susumu

doi:10.3892/ijo.15.6.1191

Cited by 27 publications

(28 citation statements)

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“…Of note, we observed up-regulation of PKR, STAT1, ISGF3␥, HLA-C, and many others. A number of groups have reported links between the IFNs and the FADD-caspase 8 axis (72)(73)(74)(75)(76). IFN and PKR, a double stranded RNA-dependent protein kinase induced by IFNs, have both been shown to signal apoptosis via FADD and caspase-8 (77)(78)(79).…”

Section: Discussionmentioning

confidence: 99%

Molecular Cross-talk between the TRAIL and Interferon Signaling Pathways

Kumar-Sinha

Varambally

Sreekumar

et al. 2002

Journal of Biological Chemistry

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TRAIL/APO-2L induces apoptosis in a variety of transformed cells and has potential as an anti-cancer therapeutic. The physiologic role of TRAIL is presumably more complex than merely activating caspase-mediated cell death. To shed light into TRAIL-mediated signaling, we used DNA microarrays to profile gene expression mediated by TRAIL in breast carcinoma cells. Primary response genes induced by TRAIL included a number of known NF-B-dependent genes such as cIAP2, A20, and E-selectin. Remarkably, global transcriptome analysis revealed that TRAIL also induced a cohort of genes related to the interferon-signaling pathway. Assessing interferon-induced gene expression suggested various points of interaction with the TRAIL signaling pathway. Interestingly, while we observed interferon-mediated up-regulation of TRAIL, we also demonstrated a concomitant TRAIL-mediated induction of interferon-␤. Combining TRAIL and interferon in vitro, synergistically induced apoptosis and caspase activation in breast cancer cells. Together, these data indicate multiple levels of molecular cross-talk between the two diverse cytokines with anti-tumor properties.TRAIL/APO-2L is a member of the tumor necrosis factor (TNF) 1 cytokine family, which are type II transmembrane proteins that share homology in their extracellular domains (1-3). A subset of these ligands is known to activate the cell death program including TNF, Fas ligand, DR3 ligand (TWEAK), and TRAIL. Of these, TRAIL has garnered the most interest therapeutically, as several studies have demonstrated in vivo tumoricidal activity in animal models without significant toxicity (4 -6). Death ligands induce apoptosis by activating their cognate receptors on the surface of cells. These death receptors are members of the TNF receptor superfamily and include TNFRI, Fas (CD95/APO-1),

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Section: Discussionmentioning

confidence: 99%

Molecular Cross-talk between the TRAIL and Interferon Signaling Pathways

Kumar-Sinha

Varambally

Sreekumar

et al. 2002

Journal of Biological Chemistry

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“…Detection of mRNA of FGFR2 by reverse transcription (RT)-polymerase chain reaction and real-time RT-polymerase chain reaction RNA preparation from the BMCs of Wt mice or FGFR2 Tg mice, cDNA synthesis, and polymerase chain reaction (PCR) were carried out as described previously [17]. Primers for the detection of mRNAs in this experiment were glyceraldehyde-3-phosphate dehydrogenase (G3PDH) (Toyobo) and FGFR2 [16].…”

Section: Reagentsmentioning

confidence: 99%

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Shigematsu

Shi²,

Okigaki³

et al. 2010

Stem Cells and Development

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Fibroblast growth factor (FGF) and FGF receptor (FGFR) are expressed in various cells including endothelial progenitor cells and hematopoietic cells. The interaction between FGF and FGFR is associated with the proliferation, migration, and survival of these cells. In this report, we examined the effects of FGFR2 signaling on hematopoiesis in immature hematopoietic cells, using mutant mice in which a constitutively active form of FGFR2 mutant was caused to be overexpressed by the Tie2 promoter (FGFR2 Tg mice). Under normal conditions, hematopoiesis of FGFR2 Tg mice and wild type (Wt) mice do not differ significantly, except for the weight and cell numbers of the thymus. However, the c-kit + Sca-1 + lineage À bone marrow cells (BMCs) of FGFR2 Tg mice facilitate the formation of colony-forming units of culture. When these BMCs were transplanted into the recipient bone marrow (intra-bone marrow-bone marrow transplantation), there was better reconstitution of donor hematopoietic cells. In the in vitro experiment, the c-kit + Sca-1 + lineage À BMCs from FGFR2 Tg mice showed fewer apoptotic cells than those from Wt mice. These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice.

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“…Regarding induction of apoptosis, however, IFNg seems to play a paradoxical role in different normal and neoplastic cell types. Whereas in normal macrophages and neoplastic myeloid and NK cells, IFNg prevents apoptosis (Lotem and Sachs, 1996;Mizuno et al, 1999;Xaus et al, 1999), it enhances apoptosis of tumour cells in malignancies such as pancreatic carcinoma, colon carcinoma and ovarian carcinoma (Adachi et al, 1999;Burke et al, 1999;Detjen et al, 2001).…”

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confidence: 99%

Malignant germ cell tumours of the testis express interferon-γ, but are resistant to endogenous interferon-γ

et al. 2003

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Cytokines possess discrepant effects on tumour cells varying from anti-to proapoptotic activities. We recently reported that testicular germ cell tumours (TGCT) express a functional form of the proinflammatory cytokine interferon-gamma (IFNg). The present study asked whether TGCT-derived IFNg influences survival or death of neoplastic germ cells. Analysis of TGCT cell lines demonstrated that they expressed and secreted IFNg, but were resistant to the endogenous IFNg since neutralisation of IFNg by a specific blocking antibody had no influence on the proliferation and/or the degree of apoptosis of tumour cells. To study mechanisms providing tumour resistance to endogenous IFNg, we analysed primary TGCT and two human TGCT cell lines (NTERA and NCCIT) for the expression of IFNg receptor and for the level of phosphorylation of the signal transducer and activator of transcription (STAT)-1. In situ hybridisation, immunocytochemistry, Western blot analysis and flow cytometry indicated that primary TGCT as well as NCCIT and NTERA cell lines expressed the heterodimeric cell surface IFNg receptor which consists of both 90-kDa a-and the 85-kDa b-chains. However, the downstream transcription factor STAT-1 was not phosphorylated constitutively, indicating that STAT-1 is not activated by the endogenous IFNg. Upon application of recombinant human IFNg in excess, however, STAT-1 was phosphorylated and the interferon regulatory factor-1 (IRF-1) was induced, suggesting that both IFNgR and STAT-1 are functionally intact in TGCT. Altogether our results suggest that despite secreting biologically active IFNg, the concentration of the endogenous IFNg is too low to stimulate the IFNgR/STAT signalling pathway in TGCT in an autocrine and/or paracrine manner.

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Apoptosis of colorectal adenocarcinoma induced by 5-FU and/or IFN-gamma through caspase 3 and caspase 8.

Cited by 27 publications

References 0 publications

Molecular Cross-talk between the TRAIL and Interferon Signaling Pathways

Molecular Cross-talk between the TRAIL and Interferon Signaling Pathways

Signaling from Fibroblast Growth Factor Receptor 2 in Immature Hematopoietic Cells Facilitates Donor Hematopoiesis After Intra-Bone Marrow–Bone Marrow Transplantation

Malignant germ cell tumours of the testis express interferon-γ, but are resistant to endogenous interferon-γ

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