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

• Regular Article
• Open access
• Published: 15 May 2001
• J Heighway2,
• H J Altermatt3,
• M Gugger4,
• A Kappeler4,
• M M Borner5,
• M van Lohuizen6 &
• …
• D C Betticher5

British Journal of Cancer volume 84, pages 1372–1376 (2001)Cite this article

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Abstract

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. http://www.bjcancer.com © 2001 Cancer Research Campaign

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Authors and Affiliations

1. Department of Clinical Research, Bern, 3010, Switzerland
   S Vonlanthen
2. Gene Function Group, Roy Castle International Centre for Lung Cancer Research, Liverpool, UK
   J Heighway
3. Pathologie Länggasse, Bern, 3010, Switzerland
   H J Altermatt
4. Institute of Pathology, University of Bern, Bern, 3010, Switzerland
   M Gugger & A Kappeler
5. Institute of Medical Oncology, Bern, 3010, Switzerland
   M M Borner & D C Betticher
6. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, 1068, CX, The Netherlands
   M van Lohuizen

Authors

1. S Vonlanthen
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2. J Heighway
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3. H J Altermatt
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4. M Gugger
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5. A Kappeler
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6. M M Borner
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7. M van Lohuizen
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8. D C Betticher
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Vonlanthen, S., Heighway, J., Altermatt, H. et al. The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression.Br J Cancer 84, 1372–1376 (2001). https://doi.org/10.1054/bjoc.2001.1791

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• Received: 29 September 2000
• Accepted: 28 February 2001
• Published: 15 May 2001
• Issue Date: 18 May 2001
• DOI: https://doi.org/10.1054/bjoc.2001.1791

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