The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression

Br J Cancer. 2001 May 18;84(10):1372-6. doi: 10.1054/bjoc.2001.1791.


Genes of the polycomb group function by silencing homeotic selector genes that regulate embryogenesis. In mice, downregulation of one of the polycomb genes, bmi-1, leads to neurological alterations and severe proliferative defects in lymphoid cells, whilst bmi-1 overexpression, together with upregulation of myc-1, induces lymphoma. An oncogenic function has been further supported in primary fibroblast studies where bmi-1 overexpression induces immortalization due to repression of p16/p19ARF, and where together with H-ras, it readily transforms MEFs. It was the aim of this study to assess the expression of bmi-1 in resectable non-small cell lung cancer (NSCLC) in association with p16 and p14ARF (=human p19ARF). Tumours (48 resectable NSCLC (32 squamous, 9 adeno-, 2 large cell, 4 undifferentiated carcinomas and 1 carcinoid); stage I, 29, II, 7, III, 12; T1, 18, T2, 30; differentiation: G1 12, G2 19, G3 17) were studied by immunohistochemistry for protein expression and by comparative multiplex PCR for gene amplification analysis. In tumour-free, normal lung tissue from patients, weak - moderate bmi-1 staining was seen in some epithelial cells, lymphocytes, glandular cells and in fibroblasts, whereas blood, endothelial, chondrocytes, muscle cells and adipocytes did not exhibit any bmi-1 expression. In tumours, malignant cells were negative/weakly, moderately and strongly positive in 20, 22 and 6 cases, respectively. As assessed by multiplex PCR, bmi-1 gene amplification was not the reason for high-level bmi-1 expression. Tumours with moderate or strong bmi-1 expression were more likely to have low levels of p16 and p14ARF (P = 0.02). Similarly, tumours negative for both, p16 and p14ARF, exhibit moderate-strong bmi-1 staining. 58% of resectable NSCLC exhibit moderate-high levels of bmi-1 protein. The inverse correlation of bmi-1 and the INK4 locus proteins expression (p16/p14ARF) supports a possible role for bmi-1 misregulation in lung carcinogenesis.

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Humans
  • Lung / cytology
  • Lung / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics*
  • Organ Specificity
  • Polycomb Repressive Complex 1
  • Polymerase Chain Reaction
  • Proteins / genetics*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics*
  • Repressor Proteins*
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p14ARF
  • Zinc Fingers


  • BMI1 protein, human
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Tumor Suppressor Protein p14ARF
  • Polycomb Repressive Complex 1