Expression and Genetic Analysis of XIAP-Associated Factor 1 (XAF1) in Cancer Cell Lines

Fong, Wai Gin; Liston, Peter; Rajcan‐Separovic, Evica; Jean, Martine St.; Craig, Constance G.; Korneluk, Robert G.

doi:10.1006/geno.2000.6364

Cited by 193 publications

(174 citation statements)

References 27 publications

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“…A recent correlation between elevated XIAP and poor prognosis along with short survival has been demonstrated in patients with acute myelogenous leukemia. 8 XIAP is highly overexpressed in many tumor cell lines of the NCI (NIH) panel 9 ; however, there is little direct evidence about the role XIAP plays in tumor initiation, growth, metastasis, and chemoresistance of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells

et al. 2005

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X-linked inhibitor of apoptosis (XIAP) is the most potent member of the inhibitor of apoptosis protein (IAP) gene family in terms of its ability to inhibit caspases and suppress apoptosis. Recent evidence has suggested that XIAP is a key determinant in chemoresistance of cancer cells. To explore a novel approach for ameliorating chemotherapy of gastric cancer, the antisense expression vector for the XIAP gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). This transfer resulted in significant downregulation of XIAP expression, decreased in vitro cell viabilities, and induced apoptosis. In transferred cells, inactive caspase-3 precursors were cleaved into the active subunits (p20 and p17) during apoptosis induced by downregulation of XIAP. The inhibitory effects of cisplatin and mitomycin C on the growth of XIAP downregulated cancer cells were significantly enhanced. In addition, this process occurred only in wild-type p53 (MKN-45), but not in mutant-type p53 (MKN-28) gastric cancer cells. The data presented suggest that downregulation of XIAP via antisense RNA can lead to apoptosis of gastric cancer cells in vitro, correlating with cellular p53 status and activation of caspase-3. This finding could lead to a potential strategy for improving the efficiency of therapies for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells

et al. 2005

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“…No matter how it occurs, the complete release of cytochrome c in the cytosol could be crucial to insure adequate strength of caspase activation despite their blockade by endogenous inhibitors such as the inhibitors of activation of proteases , often upregulated in cancer cells (Fong et al, 2000;Liston et al, 2003). Interestingly, also Mfn1 is upregulated in nonsmall-cell adenocarcinoma of the lung and in other cancer cell lines, further substantiating a role for mitochondria-shaping proteins in transformation (Chung et al, 2001).…”

Section: How Do They Go From Here To There?mentioning

confidence: 99%

The many shapes of mitochondrial death

2006

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“…At the caspase level, inhibitor of apoptosis protein (IAP) family members [c-IAP1, c-IAP2, survivin, NIAP, and X-linked IAP (XIAP)] can bind to caspase-9, caspase-7, and caspase-3 and prevent the activation of the caspase cascade (31)(32)(33)(34)(35). Among these IAP members, XIAP seems to be the most potent direct caspase inhibitor (31,34) and has been shown to be overexpressed in tumor cells (36)(37)(38)(39). The implication of XIAP overexpression in resistance to TRAIL-mediated apoptosis was recently shown for different cancer cell lines (40)(41)(42)(43).…”

Section: Introductionmentioning

confidence: 99%

Constitutively Activated Nuclear Factor-κB, but not Induced NF-κB, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells

Braeuer

Büneker

Mohr

et al. 2006

Molecular Cancer Research

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The tumor necrosis factor -related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in most, but not all, cancer cells. The molecular factors regulating the sensitivity to TRAIL are still incompletely understood. The transcription factor nuclear factor-KB (NF-KB) has been implicated, but its exact role is controversial. We studied different cell lines displaying varying responses to TRAIL and found that TRAIL can activate NF-KB in all our cancer cell lines regardless of their TRAIL sensitivity. Inhibition of NF-KB via adenoviral expression of the IKB-A super-repressor only sensitized the TRAIL-resistant pancreatic cancer cell line Panc-1. Panc-1 cells harbor constitutively activated NF-KB, pointing to a possible role of preactivated NF-KB in protection from TRAIL. Furthermore, we could reduce X-linked inhibitor of apoptosis protein (XIAP) levels in Panc-1 cells by inhibition of constitutively activated NF-KB and sensitize Panc-1 cells to TRAIL by RNA interference against XIAP. These results implicate elevated XIAP levels caused by high basal NF-KB activity in TRAIL resistance and suggest that therapeutic strategies involving TRAIL can be abetted by inhibition of NF-KB and/or XIAP only in tumor cells with constitutively

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Expression and Genetic Analysis of XIAP-Associated Factor 1 (XAF1) in Cancer Cell Lines

Cited by 193 publications

References 27 publications

Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells

Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells

The many shapes of mitochondrial death

Constitutively Activated Nuclear Factor-κB, but not Induced NF-κB, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells

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