BMI1'S maintenance of the proliferative capacity of laryngeal cancer stem cells

Head Neck. 2011 Aug;33(8):1115-25. doi: 10.1002/hed.21576. Epub 2010 Dec 6.

Abstract

Background: In laryngeal squamous cell carcinoma (SCC), CD133+ cells were found to display cancer stem cell (CSC) characteristics. BMI1 is an oncogene that plays key roles in proliferation in CSCs. However, no published reports have examined the role of BMI1 in laryngeal CSCs.

Methods: Immunofluorescence staining confirmed the coexpression of BMI1 and CD133. After sorting, real-time polymerase chain reaction (PCR) revealed BMI1 was differentially expressed in CD133+ cells. BMI1 was knocked down and proliferation, colony formation, and apoptosis assays were performed. The influence on CD133+ cells was determined by flow cytometry, sphere-formation assay, and quantitative PCR. Tumorigenicity assays were performed, and the impact on related genes was evaluated.

Results: BMI1 was highly enriched in CD133+ cells. BMI1 maintained CD133+ cell proliferation and prevented apoptosis. Gene expression analysis suggested BMI1 regulated alternate cellular pathways.

Conclusion: BMI1 was required to maintain the proliferative capacity of laryngeal CSCs, which may be a molecular target to cure patients with laryngeal SCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis / genetics*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Down-Regulation
  • Fluorescent Antibody Technique
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Mice
  • Microscopy, Confocal
  • Neoplastic Stem Cells / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sensitivity and Specificity
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • BMI1 protein, human
  • Biomarkers, Tumor
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 1