Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients

Ferreira, Carlos Gil; Valk, Paul van der; Span, Simone W.; Jonker, J.M.; Postmus, Pieter E.; Kruyt, Frank A.E.; Giaccone, Giuseppe

doi:10.1023/a:1011167113067

Cited by 104 publications

(89 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Comparable results to RCC were reported for the prognostic significance of XIAP in acute myeloid leukemia (30). Conflicting results have been reported for small cell lung carcinoma (15,31).…”

Section: Discussionmentioning

confidence: 98%

“…These findings implied that overexpression of XIAP in tumor cells may render the cells resistant to apoptotic stimuli and may survive following therapy. XIAP is expressed in normal tissues, however, overexpression of XIAP has been demonstrated in several cancers including lung cancer and prostate cancer (15,16). In addition, downregulation of XIAP sensitizes the resistant cancer cells to death receptor-or cytotoxic drug-induced apoptosis (17,18).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis

Mizutani¹,

Nakanishi²,

Li³

et al. 2007

Int J Oncol

View full text Add to dashboard Cite

Abstract. X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase-inhibitory IAP family member and a negative regulator of various apoptotic stimuli. Thus, XIAP overexpression in cancer cells may select for tumor cell survival following various cytotoxic therapeutic modalities. The anatomical staging system in renal cell carcinoma (RCC) currently provides good prognostic information, albeit insufficient. We hypothesize that overexpression of XIAP in RCC may serve as a molecular prognostic marker in RCC and improve the staging of RCC. This study examined the protein level of XIAP in lysates from surgical specimens of 109 patients with RCC and 109 normal kidney specimens from the same patients. The level of XIAP expression was quantified by Western blot analysis using non-fixed fresh frozen tissues of RCCs and normal kidneys. Results indicated that the mean level of XIAP expression was higher in RCC compared to autologous normal kidney, and the XIAP expression level in 38/109 (35%) of RCC was more than 2-fold greater than that in normal kidney tissue. In Stage I/II RCC, the mean XIAP expression level was almost identical to that detected in normal kidney, whereas XIAP expression in Stage III/IV was 2.5-fold higher than that in Stage I/II RCC. Levels of XIAP expression also correlated with the grade of RCC. Patients with RCC with low XIAP expression had a longer postoperative disease-specific survival as compared to those with high expression in the 5-year follow-up. The suggested role of XIAP in the regulation of resistance in apoptosis was examined in vitro following treatment of RCC cell lines with XIAP antisense oligonucleotide and the cells were sensitized to both Fas-mediated and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The present study demonstrates at the protein level that XIAP is overexpressed in RCC, and that high XIAP expression in RCC predicted a worse prognosis. In addition, XIAP antisense oligonucleotide sensitized RCC to Fas/TRAILinduced apoptosis. These results suggest that XIAP expression in RCC may be used as a prognostic parameter, and that downregulation or inhibition of XIAP expression in RCC may reverse immune resistance. IntroductionRenal cell carcinoma (RCC) accounts for approximately 2% of all cancer cases worldwide (1). Metastatic disease is often present at the time of diagnosis of RCC and its poor response to chemotherapy and radiotherapy determines its poor prognosis (2). Immunotherapy is relatively effective for RCC, however, the response rate is approximately 20% (3). Therefore, new therapeutic approaches are necessary for these patients with metastatic RCC.The aggressive stage of cancer is characterized by the appearance of apoptosis-resistant cells as a result of various genetic mutations and overexpression of anti-apoptotic factors. Apoptosis can be achieved by a number of ligand receptor families, commonly called death receptors and also by various drugs or stress-induced stimuli. Death receptors bind to their respectiv...

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis

Mizutani¹,

Nakanishi²,

Li³

et al. 2007

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…It is also signi®cant to note that the so-called extrinsic, caspase-8 regulated, and intrinsic, caspase-9 regulated, cell death pathways appear to act synergistically to promote cell death (Engels et al, 2000;Ferreira et al, 2000;Lacour et al, 2001), as well as promote apoptosis in a more pathwaydependent manner. For example, caspase-9/Apaf-1/ cytochrome c activation following caspase-8 activation through mediator-molecules such as BID (Gross et al, 1999b) or BAR (Zhang et al, 2000), or alternatively, the activation of caspase-8 following caspase-9 and caspase-3 activation to augment and speed cell death (Tang et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Even so, p53 can modulate and enhance the STS-induced apoptotic response to some extent. Evidence exists for p53-dependent activation of the caspase-9 apoptosome (Soengas et al, 1999), as well as an essential role for capase-8 in transcriptionindependent apoptosis triggered by p53 (Ferreira et al, 2000). Furthermore, it has recently been demonstrated that while primary, untreated neuroblastoma tumors rarely harbor p53 mutations, chemotherapeutic drug treatment can induce p53 gene mutations in neuroblastoma tumors (Tweddle et al, 2001).…”

Section: Status and Expression Of The P53 Tumor Suppressor Gene In Thmentioning

confidence: 99%

Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN

et al. 2002

View full text Add to dashboard Cite

Important roles have been suggested for caspase-8, caspase-9 and Apaf-1 in controlling tumor development and their sensitivity to chemotherapeutic agents. Methylation and deletion of Apaf-1 and CASP8 results in the loss of their expression in melanoma and neuroblastoma, respectively, while CASP9 localization to 1p36.1 suggests it is a good candidate tumor suppressor. The status of CASP9 and Apaf-1 expression in numerous neuroblastoma cell lines with/without ampli®ed MYCN and chromosome 1p36 loss-of-heterozygosity (LOH) was therefore examined to test the hypothesis that one or both of these genes are tumor suppressors in neuroblastoma. Although CASP9 is included in the region encompassing 1p36 LOH in all neuroblastoma cell lines examined, the remaining CASP9 allele(s) express a functional caspase-9 enzyme. Apaf-1 is also expressed in all neuroblastoma tumor cell lines examined. Thus, the CASP9 or Apaf-1 genes do not appear to function as tumor suppressors in MYCN ampli®ed neuroblastomas. However, *20% of the neuroblastoma cell lines with methylated CASP8 alleles are also highly resistant to staurosporine (STS)-and radiation-induced cell death, presumably because cytochrome c is not released from mitochondria. This suggests that a second, smaller subgroup of MYCN ampli®ed neuroblastoma tumors exists with defect(s) in apoptotic signaling components upstream of caspase-9 and Apaf-1. Since no consistent di erences in Bcl-2, Bcl-x L or Bax expression were seen in the STS-and radiation-resistant neuroblastomas, it suggests that a unique mitochondrial signaling factor(s) is responsible for the defect in cytochrome c release in this sub-group of tumors.

show abstract

“…For example, both IAPs were shown to be upregulated in colorectal carcinoma (Krajewska et al, 2005), a type of cancer that often carries ras oncogene (Bos et al, 1987). Furthermore, XIAP and cIAP2 are frequently upregulated in lung carcinoma (Ferreira et al, 2001;Hofmann et al, 2002), another malignancy that often carries oncogenic ras (Rodenhuis et al, 1988). In addition, expression of both IAPs tends to be elevated in prostate carcinoma (Krajewska et al, 2003), a disease that is often associated with increased levels of ErbB2 (Signoretti et al, 2000;Shi et al, 2001), an established inhibitor of anoikis (Reginato et al, 2003) and a known activator of Ras (Satoh et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells

Liu

et al. 2006

Oncogene

View full text Add to dashboard Cite

Detachment of normal epithelial cells from the extracellular matrix triggers apoptosis, a phenomenon called anoikis. Conversely, carcinoma cells tend to be relatively more anoikis-resistant than their normal counterparts, and this increased resistance represents a critical feature of the malignant phenotype. Mechanisms that control susceptibility and resistance to anoikis are not fully understood. It is now known that detachment of non-malignant epithelial cells triggers both pro-and antiapoptotic signals, and it is the balance between these signals and the duration of detachment that determine further fate of the cells. Detachment-induced antiapoptotic events delay anoikis and if cells reattach relatively soon after detachment they survive. Direct regulators of apoptosis responsible for this delay of anoikis are unknown. We found that detachment of non-malignant intestinal epithelial cells triggers upregulation of inhibitors of apoptosis protein (IAP) family, such as X-chromosome-linked inhibitor of apoptosis protein and cellular inhibitor of apoptosis-2 (cIAP2). We demonstrated that this upregulation requires detachmentdependent activation of the transcription factor nuclear factor-jB. We further observed that various IAP antagonists accelerate anoikis, indicating that upregulation of the IAPs delays detachment-triggered apoptosis. We conclude that the IAPs are important regulators of the balance between detachment-triggered life and death signals. Perhaps, not by coincidence, these proteins are often upregulated in carcinomas, tumors composed of cells that tend to be anoikis-resistant.

show abstract

Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients

Cited by 104 publications

References 36 publications

Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis

Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis

Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN

Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells

Contact Info

Product

Resources

About