Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors

Shigeishi, Hideo; Yoneda, Shingo; Taki, Masayuki; Nobumori, Takeshi; Ohta, Kouji; Higashikawa, Koichiro; Yasui, Wataru; Kamata, Nobuyuki

doi:10.3892/or.15.4.933

Cited by 16 publications

(15 citation statements)

References 28 publications

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“…Furthermore, oral SCC patients with lower CENP-F mRNA levels had a better survival rate than those with higher CENP-F mRNA levels (25). We also reported a significant correlation between CENP-F/Bub1 expression and the Ki-67 labeling index in salivary gland tumors (26,27). These results suggest the usefulness of the CENP-F gene as an additional diagnostic tool for oral SCCs and salivary gland tumors.…”

Section: Discussionsupporting

confidence: 57%

Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity

Shigeishi

Higashikawa²,

Ono³

et al. 2006

Oncol Rep

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We examined the expression of Centromere protein H (CENP-H) mRNA in 38 oral squamous cell carcinomas (SCCs), 2 epithelial dysplasias and 5 normal gingivae using the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean expression level of CENP-H mRNA was higher in oral SCCs (0.11±0.08) than epithelial dysplasias (0.03±0.01) and normal gingivae (0.027±0.01). The expression level of CENP-H mRNA was significantly higher in oral SCCs than normal gingivae (Mann-Whitney U test, P=0.005). We also found a significant association between the level of CENP-H mRNA expression and clinical stage in oral SCCs (Mann-Whitney U test, P=0.04). We next studied the expression of CENP-H in 17 oral SCCs immunohistochemically. A significant correlation between the expression levels of CENP-H protein and the Ki-67 labeling index was found (Mann-Whitney U test, P=0.005). These results indicate that human CENP-H is closely linked to the increased or abnormal cell proliferation in malignant conditions.

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Section: Discussionsupporting

confidence: 57%

Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity

Shigeishi

Higashikawa²,

Ono³

et al. 2006

Oncol Rep

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“…The expression of the centromere protein and spindle assembly checkpoint gene were reported to be significantly correlated with Ki-67 labeling index and clinical stage in primary salivary gland carcinomas (19,20). Furthermore, telomerase activity was found to be significantly higher in high-grade compared to low-grade mucoepidermoid carcinomas (21).…”

Section: Discussionmentioning

confidence: 94%

“…Recent molecular biology studies have focused on the identification of the specific molecular characteristics of salivary gland carcinomas (19)(20)(21)(22)(23). The expression of the centromere protein and spindle assembly checkpoint gene were reported to be significantly correlated with Ki-67 labeling index and clinical stage in primary salivary gland carcinomas (19,20).…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological analysis of salivary gland carcinomas and literature review

Shigeishi

Ohta

Okui

et al. 2014

Molecular and Clinical Oncology

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Malignant salivary gland tumors are rare and exhibit a broad spectrum of phenotypic heterogeneity. The objective of this study was to investigate prognostic factors in patients with salivary gland carcinomas and review the results in light of other reports. We retrospectively reviewed 40 patients with primary salivary gland carcinomas who were diagnosed and treated at our institution between 1991 and 2014. Of the 40 tumors, 19 (47.5%) were mucoepidermoid carcinomas, 11 (27.5%) were adenoid cystic carcinomas, 7 (17.5%) were acinic cell carcinomas, 2 (5.0%) were myoepithelial carcinomas and 1 (2.5%) was a squamous cell carcinoma. Clinically positive lymph nodes were present in 4 patients (10.0%). As regards clinical stage, 15 cases (37.5%) were stage I, 13 (32.5%) were stage II, 1 (2.5%) was stage III and 11 (27.5%) were stage IVA. The majority of the patients (97.5%) were treated with surgery, of whom 25 (62.5%) received surgery alone and 14 (35.0%) underwent surgery in combination with chemotherapy or chemotherapy and radiotherapy. The median follow-up time for all the patients was 48 months. The disease-specific survival rate at 5 years was 87.1%. We identified a significant correlation between poor survival rate and histological grade (intermediate/high), tumor size (T3/T4), lymph node metastasis (node-positive) and clinical stage (III/IV) using the Kaplan-Meier method (P<0.05 for each). In addition, the Cox proportional hazards regression analysis confirmed that lymph node metastasis and tumor size were independent prognostic factors for disease-specific survival (hazard ratio = 18.7 and 15.1, respectively; P=0.023 and 0.037, respectively). Furthermore, tumor size was found to be a predictive factor regarding recurrence in the multivariate logistic regression analysis (odds ratio = 8.35; P=0.025). Our results suggest that lymph node metastasis and tumor size are significant prognostic factors for patients with salivary gland carcinomas.

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“…34 In other cases it appears, paradoxically, that spindle checkpoint proteins are upregulated in tumors. [35][36][37][38] In the case of Mad2, upregulation was shown to promote tumorigenesis, suggesting that any perturbation of spindle checkpoint proteins might drive cells into genomic instability, which might in turn facilitate tumorigenesis. 39,40 Recent reports indicate that tumor suppressors like BRCA1 and oncogenes such as c-myc are involved in regulation of spindle checkpoint genes, which might account for some of their roles in oncogenesis.…”

Section: Bub1: a Multi-functional Spindle Checkpoint Proteinmentioning

confidence: 99%

Bub1: Escapades in a Cellular World

Williams

Roberts²,

Gjoerup

2007

Cell Cycle

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The spindle assembly checkpoint is an important surveillance mechanism that ensures high fidelity mitotic chromosome segregation. This is accomplished by monitoring whether sister chromatids lack tension or attachment to spindle microtubules. It is mediated by checkpoint complexes or individual proteins that inhibit the ubiquitin ligase activity of the anaphase-promoting complex/cyclosome (APC/C) via targeting of the Cdc20 regulatory subunit. The Bub1 kinase is a key spindle checkpoint regulatory protein. Bub1 also plays more pleiotropic roles. Thus, Bub1 is required for assembly of a functional inner centromere, sister chromatid cohesion via targeting of the Shugoshin protein, and metaphase congression. Evidence based on Bub1 mutations in colorectal cancers suggests it might be a driving force in tumorigenesis via generation of chromosomal instability (CIN) and aneuploidy. Recently we reported a surveillance mechanism linking loss of Bub1 to activation of the p53 pathway, specifically premature cell senescence in normal human fibroblasts. Interestingly, SV40 large T antigen (LT) targets Bub1 and this is correlated with oncogenic transformation and compromise of the spindle checkpoint. Future studies on Bub1 combining genetic approaches with analysis of LT perturbations are likely to yield further insight.

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Correlation of human Bub1 expression with tumor-proliferating activity in salivary gland tumors

Cited by 16 publications

References 28 publications

Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity

Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity

Clinicopathological analysis of salivary gland carcinomas and literature review

Bub1: Escapades in a Cellular World

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