Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival

Autor: Yip Fk, Kim Sj, No-Hee Park, Goberdhan P. Dimri, Kang Mk, Christensen R, Shin Kh, Kim Rh, Han T
Rok vydání: 2006
Předmět:
keratinocytes
Cancer Research
Tumor suppressor gene
Cell Survival
Cell
Biology
medicine.disease_cause
Sensitivity and Specificity
Cell Line
03 medical and health sciences
RNA interference
0302 clinical medicine
Proto-Oncogene Proteins
Tumor Cells
Cultured
medicine
Humans
RNA
Messenger
Bmi-1
Molecular Diagnostics
Cell Proliferation
030304 developmental biology
Polycomb Repressive Complex 1
0303 health sciences
Gene knockdown
Staining and Labeling
Oncogene
Reverse Transcriptase Polymerase Chain Reaction
Cell growth
Gene Expression Profiling
Gene Amplification
Nuclear Proteins
nutritional and metabolic diseases
oral cancer
Cell cycle
Immunohistochemistry
Gene Expression Regulation
Neoplastic
Repressor Proteins
Cell Transformation
Neoplastic
p16INK4A
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cancer cell
Immunology
Carcinoma
Squamous Cell
Cancer research
Mouth Neoplasms
Carcinogenesis
polycomb
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
DOI: 10.1038/sj.bjc.6603529
Popis: Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study was undertaken to determine the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression levels were markedly enhanced in the cells of oral squamous cell carcinomas (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi-1 expression was also detected in situ in the archived oral mucosal tissues with cancerous and precancerous histopathology, including that of mild epithelial dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation, endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK by RNA interference. After Bmi-1 knockdown, cell replication was severely retarded. However, the expression of p16(INK4A), a known cellular target of Bmi-1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1 knockdown in HOK-16B-BaP-T cells, in which the p16(INK4A)/pRb pathway was abrogated, led to immediate arrest of replication and loss of viable cells. Thus, our data suggest that Bmi-1 may act through p16(INK4A)-independent pathways to regulate cellular proliferation during oral cancer progression.
Databáze: OpenAIRE
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