Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma

Xu, Jing; Furuya, Tomoko; Cao, Xi; Liu, Xiao Li; Li, Qing Quan; Wang, Wen Juan; Xu, Jie; Xu, Zhenshan; Sasaki, Kohsuke; Liu, Xiu Ping

doi:10.1111/j.1365-2559.2010.03720.x

Cited by 12 publications

(19 citation statements)

References 36 publications

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“…Several oncogenes are known to be downregulated in tumors and their low expression predicts a poor prognosis. Clinical studies have shown that low expression of the oncoproteins Bcl-2 and Bcl-B is associated with a poor outcome of GC [32-34]. A similar “discrepancy” has also been noted for some tumor suppressor genes.…”

Section: Discussionmentioning

confidence: 74%

XB130 promotes proliferation and invasion of gastric cancer cells

et al. 2014

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BackgroundXB130 has been reported to be expressed by various types of cells such as thyroid cancer and esophageal cancer cells, and it promotes the proliferation and invasion of thyroid cancer cells. Our previous study demonstrated that XB130 is also expressed in gastric cancer (GC), and that its expression is associated with the prognosis, but the role of XB130 in GC has not been well characterized.MethodsIn this study, we investigated the influence of XB130 on gastric tumorigenesis and metastasis in vivo and in vitro using the MTT assay, clonogenic assay, BrdU incorporation assay, 3D culture, immunohistochemistry and immunofluorescence. Western blot analysis was also performed to identify the potential mechanisms involved.ResultsThe proliferation, migration, and invasion of SGC7901 and MNK45 gastric adenocarcinoma cell lines were all significantly inhibited by knockdown of XB130 using small hairpin RNA. In a xenograft model, tumor growth was markedly inhibited after shXB130-transfected GC cells were implanted into nude mice. After XB130 knockdown, GC cells showed a more epithelial-like phenotype, suggesting an inhibition of the epithelial-mesenchymal transition (EMT) process. In addition, silencing of XB130 reduced the expression of p-Akt/Akt, upregulated expression of epithelial markers including E-cadherin, α-catenin and β-catenin, and downregulated mesenchymal markers including fibronectin and vimentin. Expression of oncoproteins related to tumor metastasis, such as MMP2, MMP9, and CD44, was also significantly reduced.ConclusionsThese findings indicate that XB130 enhances cell motility and invasiveness by modulating the EMT-like process, while silencing XB130 in GC suppresses tumorigenesis and metastasis, suggesting that it may be a potential therapeutic target.

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Section: Discussionmentioning

confidence: 74%

XB130 promotes proliferation and invasion of gastric cancer cells

et al. 2014

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“…Our previous data 2 demonstrated, by immunohistochemistry, that most cancer cells in gastric carcinoma tissue lose the ability to express BCL2L10 protein, in contrast to non‐carcinoma gastric tissues. In the current study, we tested fresh specimens and cancer cell lines for BCL2L10 mRNA and protein content.…”

Section: Resultsmentioning

confidence: 93%

“…We successfully mimicked gastric cancer cells with low levels of BCL2L10 using a murine xenograft model, and found that they showed up‐regulated proliferation in vivo . Interestingly, a retrospective study also revealed a significant correlation between decreased BCL2L10 expression and larger tumour volume in gastric carcinoma 2. The results obtained by cytometry, immunoblotting and PI3K inhibition revealed that growth promotion was associated with PI3K–Akt activated rapid cell cycle progression through the G 1 /S phase, suggesting a potential mechanism of malignancy with low‐level BCL2L10.…”

Section: Discussionmentioning

confidence: 94%

“…Gastric cancer is the second most common cause of death from cancer 1. A previous study 2 demonstrated that, in contrast to non‐carcinoma gastric tissues, most cells in gastric carcinoma tissues lose BCL2L10 protein expression. Additionally, the loss of BCL2L10 protein expression predicted poor clinical outcome in gastric carcinoma patients.…”

Section: Introductionmentioning

confidence: 99%

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BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells

Cao

Long

et al. 2010

The Journal of Pathology

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The reason for and consequences of BCL2L10 down-regulation in gastric carcinoma are poorly understood. Our aim was to investigate the function of the protein BCL2L10 in gastric carcinoma. We investigated BCL2L10 expression using quantitative real-time PCR and immunoblotting. The methylation status of the BCL2L10 gene promoter was examined by bisulphite sequencing in fresh gastric normal and carcinoma tissues. We studied apoptosis and proliferation regulation in gastric cancer cell lines using flow cytometry, fluorescence staining, murine xenografting and immunoblotting. Pathway inhibitors were applied to confirm the major pathways involved in apoptosis or proliferation regulation. We observed significant correlations between lower BCL2L10 expression and CpG island hypermethylation of the BCL2L10 gene promoter in gastric carcinoma, apoptosis induced by over-expressed BCL2L10 through mitochondrial pathways, and proliferation accelerated by BCL2L10 siRNA via the PI3K-Akt signalling pathway in gastric cancer cell lines. The pro-apoptotic effect of BCL2L10 and growth promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a tumour suppressor.

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“…However, in both study the authors did not study the relation between methylation of the BCL2L10 promoter and modulation of expression of its mRNA or protein level[30]. Of note, in gastric cancer cells methylation of the BCL2L10 promoter seems to correlate with decreased expression of BCL2L10 protein level [31, 32]. Taking into account the discrepancies reported regarding the impact of BCL2L10 promoter methylation status, it appears of great interest to consider its protein rather than its mRNA expression, in agreement with a recent report by Beverly et al [33].…”

Section: Discussionmentioning

confidence: 99%

BCL2L10 is a predictive factor for resistance to Azacitidine in MDS and AML patients

Cluzeau

Robert²,

Mounier³

et al. 2012

Oncotarget

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ABSTRACT:Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment. These patients have a drastically reduced life expectancy as compared to sensitive patients. Therefore identifying predictive factors for AZA resistance is of great interest to propose alternative therapeutic strategies for non-responsive patients. We generated AZA-resistant myeloid cell line (SKM1-R) that exhibited increased expression of BCL2L10 an anti-apoptotic Bcl-2 family member. Importantly, BCL2L10 knockdown sensitized SKM1-R cells to AZA effect suggesting that increased BCL2L10 expression is linked to AZA resistance in SKM1-R. We next established in 77 MDS patients that resistance to AZA is significantly correlated with the percentage of MDS or AML cells expressing BCL2L10. In addition, we showed that the proportion of BCL2L10 positive bone marrow cells can predict overall survival in MDS or AML patients. We propose a convenient assay in which the percentage of BCL2L10 expressing cells as assessed by flow cytometry is predictive of whether or not a patient will become resistant to AZA. Therefore, systematic determination of BCL2L10 expression could be of great interest in newly diagnosed and AZA-treated MDS patients.

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Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma

Abstract: Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma.

Cited by 12 publications

References 36 publications

XB130 promotes proliferation and invasion of gastric cancer cells

XB130 promotes proliferation and invasion of gastric cancer cells

BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells

BCL2L10 is a predictive factor for resistance to Azacitidine in MDS and AML patients

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