Correlation between reduced expression of the spindle checkpoint protein BubR1 and bad prognosis in tonsillar carcinomas

Hannisdal, Kirsten; Burum-Auensen, Espen; Schjølberg, Aasa R.; Angelis, Paula M. De; Clausen, O. P. F.

doi:10.1002/hed.21342

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…34 Our study failed to demonstrate a statistically significant correlation between Ki-67 labeling index and BUBR1 expression. This finding does not support the association between overexpression of BUBR1 and increased proliferative activity previously reported not only in gastric, 19 bladder, 21 colorectal, 17 and hepatocellular cancer, 27 but also in tonsillar carcinoma 34 ; however, it is not in contrast with our above-mentioned results that suggest a favorable role of BUBR1 in the prognosis of oral cancer. This assumption, in fact, would have been difficult to reconcile with a high proliferative index, which is a well-known negative prognostic factor in a variety of tumors, including OSCC.…”

Section: Discussioncontrasting

confidence: 60%

“…BUBR1 stained the cytoplasm of normal oral epithelial cells, as previously described by BurumAuensen et al 36 In OSCC, subcellular localization of BUBR1 remained mainly confined to the cytoplasm, confirming previous observations. 34,37 In the normal epithelium, sporadic cells in the basal and parabasal layers occasionally exhibited weak staining. In the dysplastic epithelium neighboring squamous cell carcinomas, BUBR1-positive cells were more frequent and were also detectable above the parabasal layer (see Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…32 Qi et al 33 correlated Aurora B expression with cell proliferation, histologic differentiation, and metastasis in OSCC, suggesting that it may be involved in tumor progression. Hannisdal et al 34 first examined the expression of BUBR1 and MAD2 in tonsillar carcinoma, showing a strong correlation between reduced expression of BUBR1 and poor prognosis. On the contrary, in their study on OSCC, Lira et al 35 found that higher expression of BUBR1 was associated with lymph node metastases and shorter survival, and that it could be related to human papillomavirus (HPV) status.…”

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confidence: 98%

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BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival

et al. 2010

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Section: Discussioncontrasting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

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confidence: 98%

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BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival

et al. 2010

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“…Previous studies have demonstrated that upregulation of BubR1 in ovarian and tonsillar cancers was associated with lymph node metastasis, tumor grade and stage (11,25). We examined the relationship between the clinical histopathological features and BubR1 expression in the ESC cases (Table I).…”

Section: High Expression Of Bubr1 In Clinical Esophageal Cancer Samplesmentioning

confidence: 99%

Abnormal expression of the mitotic checkpoint protein BubR1 contributes to the anti-microtubule drug resistance of esophageal squamous cell carcinoma cells

Liu

Song

et al. 2012

Oncology Reports

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Esophageal cancer is a common malignancy with a high mortality rate. The lack of effective chemotherapy and a means to overcome drug resistance leads to the predictable failure of esophageal cancer treatment. Mitotic checkpoint proteins play a critical role in regulating the cell cycle and proliferation. Abnormal expression of the mitotic checkpoint protein BubR1 has been reported in several types of cancers. In this study, we investigated the role of BubR1 in conferring resistance of esophageal cancer cells to anti-microtubule drugs. Using quantitative real-time PCR analysis on 50 samples of paired esophageal squamous cell cancer (ESC) tissues and adjacent non-cancerous tissues, we found that 72% (36 of 50) of the analyzed ESC samples exhibited high expression levels of BubR1, which was also confirmed in ESC cell lines. ESC cells with high levels of BubR1 were less sensitive to the anti-microtubule drugs paclitaxel and nocodazole. Recombinant adenovirus-mediated enforced expression of BubR1 in relatively sensitive ESC cell lines resulted in increased resistance to paclitaxel. Conversely, RNAi-mediated knockdown of BubR1 restored ESC cell sensitivity to paclitaxel. Cell cycle analysis indicated that the sub-G1 population increased in the ESC cells with reduced BubR1 levels. Taken together, our results suggest that upregulation of BubR1 expression may be associated with ESC resistance to paclitaxel treatment. Thus, BubR1 may serve as a potential chemosensitizing target to overcome chemoresistance.

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“…In contrast, another study shows that overexpression of BubR1 was associated with a less advanced tumor stage, but patients with overexpression of BubR1 showed shorter recurrence-free survival than those without it, making BubR1 a promising prognostic marker in patients with OSCC [64]. Curiously, the proliferation marker Ki-67 did not demonstrate a statistical significant correlation with BubR1 expression, contrasting with a previous report in patients with tonsillar carcinomas [65]. Another SAC protein that was also found to be overexpressed in oral carcinoma is the Aurora B kinase.…”

Section: Spindle Assembly Checkpoint and Oral Squamous Cell Carcinomamentioning

confidence: 95%

An Overview of the Spindle Assembly Checkpoint Status in Oral Cancer

Teixeira

Silva

Reis

et al. 2014

BioMed Research International

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Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20.

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Correlation between reduced expression of the spindle checkpoint protein BubR1 and bad prognosis in tonsillar carcinomas

Abstract: We have shown that BubR1 expression is a novel and strong prognostic factor in tonsillar carcinomas, giving additional information to the TNM stage and other known prognostic factors.

Cited by 8 publications

References 47 publications

BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival

BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival

Abnormal expression of the mitotic checkpoint protein BubR1 contributes to the anti-microtubule drug resistance of esophageal squamous cell carcinoma cells

An Overview of the Spindle Assembly Checkpoint Status in Oral Cancer

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