Bmi1 regulates cell fate via tumor suppressor WWOX repression in small‐cell lung cancer cells

• Published in: Cancer science Vol. 102; no. 5; pp. 983 - 990
• Main Authors: Kimura, Masaki, Takenobu, Hisanori, Akita, Nobuhiro, Nakazawa, Atsuko, Ochiai, Hidemasa, Shimozato, Osamu, Fujimura, Yu‐ichi, Koseki, Haruhiko, Yoshino, Ichiro, Kimura, Hideki, Nakagawara, Akira, Kamijo, Takehiko
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011; Blackwell
• Subjects: Aged; Apoptosis - genetics; Biological and medical sciences; Biomarkers, Tumor; Cell Lineage; Cells, Cultured; Chromatin Immunoprecipitation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Neoplasm Staging; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oxidoreductases - genetics; Oxidoreductases - metabolism; Pneumology; Polycomb Repressive Complex 1; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Small Cell Lung Carcinoma - genetics; Small Cell Lung Carcinoma - metabolism; Small Cell Lung Carcinoma - pathology; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Tumors of the respiratory system and mediastinum; WW Domain-Containing Oxidoreductase; Lung disease; Respiratory disease; Lung cancer; Bonchopulmonary small cell carcinoma; Malignant tumor; Repression; Cancerology; BMI1 gene; C-Onc gene; Bronchus disease; Suppressive cell; Tumor cell; Protooncogene; WWOX gene; Cancer; Tumor suppressor gene
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2011.01891.x

Mortality from lung cancer is important worldwide. Recently, epigenetic aberration of lung cancer, not only genomic DNA methylation but also chromatin modification, has become an important target for lung cancer research, although previous research has demonstrated that lung cancer develops as a result of both environmental and genetic factors. Here, we demonstrated that an epigenetic regulator/polycomb group protein Bmi1 is more highly expressed in small‐cell lung cancer (SCLC) than in non‐small‐cell lung cancer by immunohistochemical analysis. In vitro experiments indicated that Bmi1 reduction by lentivirus‐derived shRNA significantly suppressed proliferation, colony formation and in vivo tumor formation. Importantly, apoptosis was induced by Bmi1 depletion in small‐cell lung cancer cells. Furthermore, a tumor suppressor WWOX was identified as a Bmi1 target in the cells by a chromatin immunoprecipitation assay and a quantitative real‐time PCR assay; WWOX had a role as a tumor suppressor in SCLC cells; therefore, the Bmi1/WWOX pathway could be a new candidate for a new therapeutic approach for SCLC. (Cancer Sci 2011; 102: 983–990)