Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance

Kikuchi, Junko; Kinoshita, Ichiro; Shimizu, Yasushi; Kikuchi, Eiki; Konishi, Jun; Oizumi, Satoshi; Kaga, Kichizo; Matsuno, Yoshihiro; Nishimura, Masaharu; Dosaka‐Akita, Hirotoshi

doi:10.1002/cncr.25128

Cited by 83 publications

(64 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 EZH2 up-regulation reportedly promoted tumor growth both in vitro and in vivo, [13][14][15][16][17][18][19][20] and it is present in several cancers in the clinical setting, including melanoma, lymphoma, prostate cancer, and breast cancer. 29 It also has been demonstrated that EZH2 is useful as a potential biomarker to distinguish aggressive breast tumors from more benign tumors.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Recent studies have demonstrated that EZH2 is frequently overexpressed in several human epithelial cancer types, including prostate cancer, inflammatory breast cancer, gastric cancer, nonsmall cell lung cancer, esophageal cancer, salivary adenoid cystic carcinoma, recurrent nasopharyngeal carcinoma, and oral cancer, and it has been linked to a poor prognosis in patients with those cancers. [13][14][15][16][17][18][19][20] In addition, in our prior study, we observed that high EZH2 levels frequently were correlated with oral cancer development in patients with oral leukoplakia. 21 Together, the previous studies suggest that EZH2 may be a key oncoprotein involved in tumor initiation and progression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Cao

Feng

Cui

et al. 2011

Cancer

View full text Add to dashboard Cite

BACKGROUND:The authors previously observed that enhancer of zeste homolog 2 (EZH2) overexpression was associated significantly with the development of oral cancer. In the current study, they investigated whether EZH2 can function as a prognostic predictor for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Expression levels of EZH2 in HNSCC cells were detected using reverse transcriptase-polymerase chain reaction (PCR) and Western blot analyses. In addition, the effects of EZH2 ablation on the proliferation and invasion of HNSCC cells were investigated through small interfering RNA (siRNA)-mediated knockdown. Real-time PCR and immunohistochemistry were used to evaluate EZH2 and cyclin D1 expression in 46 HNSCC samples, and the expression levels also were re-evaluated in 124 independent samples by immunohistochemistry. RESULTS: EZH2 expression was elevated remarkably in HNSCC specimens and cell lines. Upon EZH2 silencing, the proliferation and invasion of HNSCC cells were remarkably suppressed. EZH2 expression frequently was correlated with cyclin D1 expression (P ¼ .034) and tumor differentiation (P ¼ .020). In addition, both EZH2 messenger RNA levels and EZH2 protein levels were strongly associated with signs of histologic severity (P ¼ .012 and P ¼ .032, respectively). Univariate analysis revealed that high EZH2 expression was associated with worse overall survival (P ¼ .001) and disease-free survival (P ¼ .002). The combined expression of EZH2 and cyclin D1 had superior prognostic ability for patients with HNSCC than the expression of either marker alone. In multivariate analysis, EZH2 expression was identified as an independent predictor of overall and disease-free survival. CONCLUSIONS: The current results indicated that EZH2 is an independent prognostic indicator for patients with HNSCC. In addition, an analysis of the combined expression of EZH2 and cyclin D1 can serve as a more powerful prognostic predictor for patients with HNSCC. Cancer 2012;118:2858-71.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

Cao

Feng

Cui

et al. 2011

Cancer

View full text Add to dashboard Cite

show abstract

“…10 However, one group reported that Bmi-1 expression wasn't a significant prognostic factor, and was not correlated with any clinical pathological factors, only relative with early pathologic tumor classification in NSCLC. 11 Based on these controversial findings, further exploring the role of Bmi-1 in progression of lung cancer is necessary.…”

Section: Introductionmentioning

confidence: 99%

Bmi-1 expression modulates non-small cell lung cancer progression

Xiong

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

y These authors equally contributed to this work.Keywords: Bmi-1, EMT, invasion, metastasis, NSCLC, progression Abbreviations: NSCLC, non-small cell lung cancer; EMT, epithelial-mesenchymal transition; Bmi-1, B lymphoma Mo-MLV insertion region 1 homolog; IHC, immunohistochemistry; FBS, fetal calf serum; qRT-PCR, quantitative real-time PCR.Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression.

show abstract

“…[4][5][6] Deregulation of the EZH2-H3K27me3 pathway may also occur by other mechanisms, with over-expression of EZH2 associated with poor outcome in a range of solid tumours. [7][8][9] In this study, we set out to determine the prevalence and the prognostic value of EZH2 Y641 variants in a large cohort of patients with FL, and the relationship between mutation and EZH2 and H3K27me3 expression. Lymph node samples from 221 patients with FL were available from the tissue archive at St Barts and London Hospital (London Research Ethical Committee (05/Q0605/140)).…”

mentioning

confidence: 99%