Expression and methylation of CASP8 in neuroblastoma: Identification of a promoter region

Banelli, Barbara; Casciano, Ida; Croce, Michela; Vinci, Angela Di; Gelvi, Ilaria; Pagnan, Gabriella; Brignole, Chiara; Allemanni, Giorgio; Ferrini, Silvano; Ponzoni, Mirco; Romani, Massimo

doi:10.1038/nm1202-1333

Cited by 74 publications

(70 citation statements)

References 12 publications

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“…However, this finding does not deny the possibility that the other IRF-1-and STAT-1-binding sites may play a role in vivo in a more complex nuclear environment. Previous reports pointed out the importance of STAT-1 in the regulation of caspase-8 gene by IFN-g, since STAT-1-deficient T cells 21 or U3A cells 12 are resistant to apoptosis due to their lack of caspase-8 expression, and could not be induced to express caspase-8 by IFN-g. A recent report indicated that a GAS site within a caspase-8 promoter, similar to that identified by us, 14 plays an important role in caspase-8 gene regulation. 13 In view of the complexity of the caspase-8 genomic region, and the existence of several caspase-8 isoforms, 4,5,22,23 the presence of other caspase-8 promoter(s), possibly regulating inducible and/or constitutive expression cannot be definitively ruled out.…”

Section: Dear Editorsupporting

confidence: 70%

“…14 These observations led us to the first identification of a 1.2 kb DNA element, located 5 0 to the first exon of caspase-8 gene, which acts as a promoter in NB cell lines that express caspase-8, but not in NB cells that lack constitutive expression of this gene. 14 Here, we studied the mechanisms of caspase-8 gene regulation by IFN-g in the SH-SY-5Y NB cells, which showed virtually no constitutive expression of caspase-8. The treatment of SH-SY-5Y cells with IFN-g for 48 h induced a strong caspase-8 expression (Figure 1a).…”

Section: Dear Editormentioning

confidence: 99%

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Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE)

Casciano¹,

Ambrosis

Croce

et al. 2003

Cell Death Differ

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Section: Dear Editorsupporting

confidence: 70%

Section: Dear Editormentioning

confidence: 99%

Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE)

Casciano¹,

Ambrosis

Croce

et al. 2003

Cell Death Differ

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“…The strategy of selecting low producing IFN-g-transfected NB cells for this study was followed to prevent loss of transfectants, as already described by others (Coze et al, 1995;Ucar et al, 1995), due to the potent induction of NB tumour cell differentiation (Ponzoni et al, 1992;Ponzoni et al, 1993;Montaldo et al, 1994) and sensitisation to apoptosis (Fulda et al, 2001;Banelli et al, 2002;Fulda and Debatin, 2002) caused by high level secretion of the cytokine. The IFN-g-transfected NB cell lines described here have been maintained in culture for prolonged period of time without substantial changes in their characteristics.…”

Section: Discussionmentioning

confidence: 99%

Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

et al. 2004

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Interferon-g (IFN-g) directs T helper-1 cell differentiation and mediates antitumour effects in preclinical models. However, high-dose IFN-g is toxic in vivo, and IFN-g-transfected neuroblastoma (NB) cells secreting high amounts of the cytokine may be lost due to cell apoptosis or differentiation. Two human NB cell lines (ACN and SK-N-BE2(c)) differing as to genetic and phenotypic features were transfected with the human IFN-g gene and selected on the grounds of the low concentrations of IFN-g produced. In both IFN-gtransfected cell lines, autocrine and paracrine activation of IFN-g-mediated pathways occurred, leading to markedly reduced proliferation rate, to increased expression of surface HLA and CD40 molecules and of functional TNF binding sites. ACN/IFN-g cells showed a significantly delayed tumorigenicity in nude mice as compared to parental cells. ACN/IFN-g tumours were smaller, with extensive necrotic area as a result of a damaged and defective microvascular network. In addition, a significant reduction in the proliferation index was observed. This is the first demonstration that IFN-g inhibits in vivo proliferation of NB cell by acting on the tumour cell itself. This effect adds to the immunoregulatory and antiangiogenic activities operated by IFN-g in syngeneic tumourbearing hosts.

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“…While there is controversy as to whether survivin directly inhibits caspases, XIAP is the major inhibitor of caspase-9 and caspase-3 in cells (Takahashi et al 1998). Neuroblastomas often delete caspase-8, leaving caspase-9 and caspase-3 intact to interact with and be inhibited by XIAP (Teitz et al 2000;Banelli et al 2002). In all the neuroblastoma cell lines examined, UCN-01 efficiently eliminated this inhibition and caspases were activated.…”

Section: Discussionmentioning

confidence: 99%

UCN‐01 alters phosphorylation of Akt and GSK3β and induces apoptosis in six independent human neuroblastoma cell lines

Shankar¹,

Krupski²,

Parashar³

et al. 2004

Journal of Neurochemistry

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In this study we evaluated UCN-01, a small molecule that inhibits protein kinases by interacting with the ATP-binding site, as a potential anti-cancer agent for neuroblastoma. UCN-01 was effective at inducing apoptosis in six neuroblastoma cell lines with diverse cellular and genetic phenotypes. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) assays, detection of active caspase-3 and cleaved poly ADP-ribose polymerase (PARP) confirmed that UCN-01 induced apoptosis. Cell cycle analysis determined that the UCN-01 treated cells accumulated in S phase by 16 h. Unlike vinblastine and docetaxel that increased survivin expression, UCN-01 treatment did not increase X-linked inhibitor of apoptosis protein (XIAP) and survivin levels. Analysis of specific phosphoepitopes on chk1/2, Akt, and GSK3b following UCN-01 treatment determined that there was no significant change in phospho-chk1/2. However, there was decreased immunoreactivity at Ser473 and Thr308 of Akt and Ser9 of GSK3b by 4 h indicating that the Akt survival pathway and downstream signalling was compromised. Thus, UCN-01 was effective at inducing apoptosis in neuroblastoma cell lines. Keywords: Akt, apoptosis, GSK3b, neuroblastomas, staurosporine, survivin, 7-hydroxystaurosporine (UCN-01). Neuroblastoma is the most common malignancy of infancy and constitutes 50% of all childhood cancers (Gale et al. 1982;Young et al. 1986;Taylor and Locker 1990;Brodeur and Castleberry 1997). Some neuroblastomas may be cured by minimal therapy; however, there is no effective treatment for many advanced and metastatic neuroblastomas (Brodeur and Castleberry 1997). In addition, present treatments for neuroblastoma have significant morbidity (Brodeur and Castleberry 1997). Among the specific biological abnormalities that correlate with poor clinical outcome and aggressiveness of the tumor are nuclear DNA content, near diploidy or tetraploidy (Taylor et al. 1988;Taylor and Locker 1990;Gestblom et al. 1995), deletion of the short arm of chromosome 1 (1p) (Westermann and Schwab 2002), N-myc amplification (Taylor and Locker 1990), loss of Bcl-2 (Reed et al. 1991), insensitivity to radiation (Halperin et al. 1999), and increased expression of the inhibitor-of-apoptosis (IAP) family member, survivin (Adida et al. 1998;Azuhata et al. 2001). While these factors predict therapeutic outcome, there are specific biological determinants, such as components of the apoptotic cascade, that may be prognostic indicators for drug resistance (Emran et al. 2002;Gallo et al. 2003;Iolascon et al. 2003). Therefore, new and novel therapies with a biological rationale are urgently needed for this fatal disease.Members of the IAP family bind to and inhibit caspases and suppress cell death in cancer. Presently, there are eight mammalian IAP family members that include survivin, neuronal apoptosis inhibitor protein (NAIP), BIR-repeatcontaining ubiquitin-conjugating enzyme (BRUCE), livin, ILP-2, cIAP-1, cIAP-...

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Expression and methylation of CASP8 in neuroblastoma: Identification of a promoter region

Cited by 74 publications

References 12 publications

Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE)

Expression of the caspase-8 gene in neuroblastoma cells is regulated through an essential interferon-sensitive response element (ISRE)

Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

UCN‐01 alters phosphorylation of Akt and GSK3β and induces apoptosis in six independent human neuroblastoma cell lines

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