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Tumor Biology

, Volume 34, Issue 6, pp 3807–3815 | Cite as

Regulation of BMI1 Polycomb gene expression in histological grades of invasive ductal breast carcinomas and its correlation with hormone receptor status

  • M. V. S. Parvathi
  • P. Balakrishna Murthy
  • M. Vennila
  • B. V. Suresh
Research Article

Abstract

BMI1 is the first functional mammalian Polycomb group (PcG) proto-oncogene involved in multiple biological processes. Regulation of B cell-specific Moloney murine leukaemia virus integration site 1 (BMI1) expression with increase in histological grades of breast carcinoma in correlation with hormone receptor status was studied in 60 Indian breast cancer patient's formalin-fixed paraffin-embedded tissue blocks. Relative expression of BMI1 was studied using real-time PCR. Immunohistochemistry explained the distribution of hormone receptor markers. Correlation of BMI1 gene expression with oestrogen receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2/neu status was analysed using Hex—protein docking tool. The hormone receptor expression was reduced with increasing grades of breast tumour. BMI1 gene expression was downregulated (real-time polymerase chain reaction analysis). Docking analysis explained the correlation between BMI1 and PR expression. BMI1 gene was co-regulated (down) with PR in the invasive ductal breast carcinoma with relative progression explicating it a diagnostic biomarker for ductal carcinoma of the breast.

Keywords

Immunohistochemistry Hormone receptor interaction BMI1 RT-PCR profiling BMI1–PR Hex protein docking 

Notes

Acknowledgments

We express our gratitude to Dr. A. Sundaram, Director (Retd.), Institute of Pathology, MMC, Chennai, India, for issuing tissue blocks for the study. We thank the Management of International Institute of Biotechnology And Toxicology, Padappai (601 301, Kancheepuram District, Tamil Nadu, India) for their continuous funding and support throughout the study period.

Conflicts of interest

None

References

  1. 1.
    Ma XJ, Salunga R, Tuggle JT, et al. Gene expression profiles of human breast cancer progression. PNAS. 2003;100(10):5974–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.PubMedCrossRefGoogle Scholar
  3. 3.
    Gasparini G, Pozza F. Evaluating the potential usefulness of new prognostic and predictive indicators in node negative breast cancer patients. J Natl Cancer Inst. 1993;85:1206–19.PubMedCrossRefGoogle Scholar
  4. 4.
    Haupt Y, Alexander WS, Barri G, et al. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Emu-myc transgenic mice. Cell. 1991;65:753–63.PubMedCrossRefGoogle Scholar
  5. 5.
    Van der Lugt NM, Domen J, Linders K, et al. Posterior transformation, neurological, abnormalities, and severe hematopoitetic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. Genes Dev. 1994;8:757–69.PubMedCrossRefGoogle Scholar
  6. 6.
    Vonlanthen S, Heighway J, Altermatt HJ, 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. 2001;84:1372–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhang F, Sui L, Xin T. Correlations of BMI-1 expression and telomerase activity in ovarian cancer tissues. ExpOncol. 2008;30:70–4.Google Scholar
  8. 8.
    Masashi S, Kazuhito Y, Toshiya Y, et al. BMI-1 is highly expressed in M0-subtype acute myeloid leukemia. Int J Hematol. 2005;82:42–7.CrossRefGoogle Scholar
  9. 9.
    Li-Bing S, Mu-Sheng Z, Wen-Ting L, et al. Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res. 2006;66:6225–32.CrossRefGoogle Scholar
  10. 10.
    Dimri GP, Martinez JL, Jacobs JJ, et al. The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res. 2002;62:4736–45.PubMedGoogle Scholar
  11. 11.
    Hongjuan C, Bo H, Tai L, et al. Bmi-1 is essential for the tumourigenicity of neuroblastoma cells. Am J Pathol. 2007;170:1370–8.CrossRefGoogle Scholar
  12. 12.
    Silva J, García V, García JM, et al. Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients. Breast Cancer Research. 2007;9:R55.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu L, Andrews LG, Tollefsbol TO. Loss of the human polycomb group protein BMI1 promotes cancer-specific cell death. Oncogene. 2006;25:4370–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Lee K, Adhikary G, Balasubramanian S, et al. Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis. J Invest Dermatol. 2008;128:9–17.PubMedCrossRefGoogle Scholar
  15. 15.
    Choi YJ, Choi YL, Cho EY, et al. Expression of Bmi-1 protein in tumour tissues is associated with favorable prognosis in breast cancer patients. Breast Cancer Res Treat. 2009;113:83–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Clarke MF, Fuller M. Stem cells and cancer: two faces of eve. Cell. 2006;124:1111–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Sparmann A, Van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer. 2006;6:846–56.PubMedCrossRefGoogle Scholar
  18. 18.
    Van de Vijver MJ, He YD, Van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRefGoogle Scholar
  19. 19.
    Saeki M, Kobayashi D, Tsuji N, et al. Diagnostic importance of over expression of Bmi-1 mRNA in early breast cancers. Int J Onc. 2009;35:511–5.Google Scholar
  20. 20.
    Engelsen IB, Mannelqvist M, Stefansson IM, et al. Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma. Br J Cancer. 2008;98:1662–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Alexandra MP, Bastiaan E, Asheeta AP, et al. Bmi1 regulates stem cells and proliferation and differentiation of committed cells in mammary epithelium. Curr Biol. 2008;18:1094–9.CrossRefGoogle Scholar
  22. 22.
    Wei-J G, Mu-Sheng Z, Ajay Y, et al. Mel-18 acts as a tumour suppressor by repressing Bmi-1 expression and down-regulating Akt activity in breast cancer cells. Cancer Res. 2007;67(11):5083–9.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • M. V. S. Parvathi
    • 1
  • P. Balakrishna Murthy
    • 1
  • M. Vennila
    • 2
  • B. V. Suresh
    • 3
  1. 1.International Institute of Biotechnology and Toxicology (IIBAT)PadappaiIndia
  2. 2.Government Mohan Kumarmangalam Medical CollegeSalemIndia
  3. 3.GandipalemIndia

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