Role of IRF‐1 and caspase‐7 in IFN‐γ enhancement of Fas‐mediated apoptosis in ACHN renal cell carcinoma cells

Tomita, Yoshihiko; Bilim, Vladimir; Hara, Noboru; Kasahara, Takashi; Takahashi, Kota

doi:10.1002/ijc.10956

Cited by 53 publications

(27 citation statements)

References 53 publications

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“…Thus, although most focus on the role of IRF transcription factors as cell-cycle regulators and proapototic proteins has been on IRF-1 , these results suggest that ICSBP activates apoptosis and possesses more potent growth-inhibitory effects on lens carcinoma cells than IRF-1. Taken together with the enhanced expression of ICSBP and IRF-1 in DT mouse lens, our results are in line with other studies showing that apoptosis is induced in many tumor cell types through transcriptional activation of caspase-1 gene by IRF-1 (Horiuchi et al, 1999;Kano et al, 1999;Detjen et al, 2001;Tomita et al, 2003;Bowie et al, 2004) and ICSBP (Liu and Abrams, 2003).…”

Section: Discussionsupporting

confidence: 92%

Interferon-γ induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors

Egwuagu

et al. 2006

Oncogene

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We have developed an epithelial cell carcinoma model for studying efficacy of IFNc gene therapy and have identified components of IFNc-signaling pathway responsible for its direct anti-tumor actions. The tumor results from ectopic expression of SV40 Large T-Antigen (SV40 T-Ag) oncogene in lens of transgenic mouse (aT3) and complete regression of the tumor is induced by targeting expression of IFNc into malignant lens cells. Inflammatory cells are absent in lens of aT3 or DT (co-expressing IFNc and SV40-T-Antigen) mice and the transformed lens cells are non-immunogenic, suggesting non-involvement of immunologic cells. We show that IFNc has direct growth-inhibitory effects on tumor cells, induces death of tumor cells by apoptosis and that these effects are mediated by two transcription factors, IRF-1 (interferon-regulatory factor-1) and ICSBP (interferon-consensus sequence-binding protein) induced by IFNc. Furthermore, stable transfection with ICSBP or IRF-1 construct inhibits lens carcinoma cell growth by upregulating Caspase-1, p21 WAF1 and p27 expression. In contrast, tumor progression in aT3 lens correlates with inhibition of IRF-1 and ICSBP expression. Our results suggest that IFNc gene therapy maybe effective in malignant diseases for which DNA tumor viruses are etiologic agents and that antitumor actions of IRF-1/ ICSBP can be exploited therapeutically to circumvent adverse clinical effects associated with IFN therapy.

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Section: Discussionsupporting

confidence: 92%

Interferon-γ induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors

Egwuagu

et al. 2006

Oncogene

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“…In contrast, the IFNg-induced increase in CD95-mediated apoptosis is partially abrogated in the presence of antisense IRF1 oligodeoxynucleotide (Tomita et al, 2003). Even though CD95 can be induced directly by IFNg (Der et al, 1998), it was considered interesting to determine whether IRF1 also plays a role in CD95 upregulation.…”

Section: Discussionmentioning

confidence: 99%

Interferons α and γ induce p53-dependent and p53-independent apoptosis, respectively

et al. 2004

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Type I interferon (IFN) enhances the transcription of the tumor suppressor gene p53. To elucidate the molecular mechanism mediating IFN-induced apoptosis, we analysed programmed cell death in response to type I (IFNa) or type II (IFNc) treatment in relation to p53 status. In two cell lines (MCF-7, SKNSH), IFNa, but not IFNc, enhanced apoptosis in a p53-dependent manner. Furthermore, only IFNa upregulated p53 as well as p53 target genes (Noxa, Mdm2 and CD95). The apoptotic response to IFNa decreased in the presence of ZB4, an anti-CD95 antibody, suggesting that CD95 is involved in this process. When p53 was inactivated by the E6 viral protein or the expression of a p53 mutant, IFNa-induced apoptosis and p53 target genes upregulation were abrogated. Altogether these results demonstrate that p53 plays a pivotal role in the IFNa-induced apoptotic response. IFNa-induced PML was unable to recruit p53 into nuclear bodies and its downregulation by siRNA did not alter CD95 expression. In contrast, IFNc-induced apoptosis is p53-independent. CD95 and IFN-regulatory factor 1 (IRF1) are directly upregulated by this cytokine. Apoptotic response to IFNc is decreased in the presence of ZB4 and strongly diminished by IRF1 siRNA, implicating both CD95 and IRF1 in IFNc-induced apoptotic response. Taken together, these results show that in two different cell lines, IFNa and IFNc, induce p53-dependent -independent apoptosis, respectively. Oncogene (2005) 24, 605-615.

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“…RNA was subjected to reverse transcription polymerase chain reaction (RT-PCR) analysis as described earlier. 9 To synthesize first-strand cDNA, 1 mg of the total RNA was reverse-transcribed using a firststrand cDNA Synthesis Kit (Roche Diagnostics, Tokyo, Japan). The first-strand DNA was then amplified by PCR using the primers shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Suzuki

Nishiyama

Hara

et al. 2007

Prostate Cancer Prostatic Dis

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The metabolic pathways of androgens and processes by which androgens induce re-growth after androgen deprivation therapy in prostate cancer have not been fully elucidated. In this study, finasteride decreased PSA secretion in medium containing testosterone, androstenedione, androstenediol and dehydroepiandrosterone, whereas dihydrotestosterone (DHT)-and hydroxyflutamide-induced PSA production was not inhibited by finasteride in LNCaP-FGC cells. The present data show that adrenal androgen precursors do not directly interact with androgen receptors (ARs) but are converted to DHT via the intraprostatic metabolic pathways, resulting in the induction of LNCaP activity. This is the first report confirming this mechanism experimentally and also suggest the use of combined therapies that target ARs and prevent the formation of DHT within prostate cancer cells to achieve optimal therapeutic efficacy.

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Role of IRF‐1 and caspase‐7 in IFN‐γ enhancement of Fas‐mediated apoptosis in ACHN renal cell carcinoma cells

Cited by 53 publications

References 53 publications

Interferon-γ induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors

Interferon-γ induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors

Interferons α and γ induce p53-dependent and p53-independent apoptosis, respectively

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

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