Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Role of Nuclear Factor-κB in female Breast Cancer: A Study in Indian Patients

  • Jana, Debarshi (Comprehensive Breast Service and Breast Cancer Research Unit, Breast Service, Institute of Post Graduate Medical Education and Research (IPGME and R) and Seth Sukhlal Karnani Memorial Hospital (SSKM)) ;
  • Das, Soumen (Comprehensive Breast Service and Breast Cancer Research Unit, Breast Service, Institute of Post Graduate Medical Education and Research (IPGME and R) and Seth Sukhlal Karnani Memorial Hospital (SSKM)) ;
  • Sarkar, Diptendra Kumar (Comprehensive Breast Service and Breast Cancer Research Unit, Breast Service, Institute of Post Graduate Medical Education and Research (IPGME and R) and Seth Sukhlal Karnani Memorial Hospital (SSKM)) ;
  • Mandal, Syamsundar (Department of Epidemiology and Biostatistics, Chittaranjan National Cancer Institute) ;
  • Maji, Abhiram (Department of General Surgery, Calcutta National Medical College) ;
  • Mukhopadhyay, Madhumita (Comprehensive Breast Service and Breast Cancer Research Unit, Breast Service, Institute of Post Graduate Medical Education and Research (IPGME and R) and Seth Sukhlal Karnani Memorial Hospital (SSKM))
  • Published : 2012.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Introduction: The nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-${\kappa}B$ /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. Materials and Methods: In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. Results: NF-${\kappa}B$/p65 was significantly associated with advanced stage, large tumor size (${\geq}5$ cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-${\kappa}B$/p65 expression was more frequent in patients with a high NPI ($NPI{\geq}5.4$, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p = 0.002). Conclusion: NF-${\kappa}B$/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-${\kappa}B$/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-${\kappa}B$ /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-${\kappa}B$ positive tumors need to be treated aggressively.

Keywords

References

  1. Almasri NM, Al Hamad M (2005). Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan. Breast Cancer Res, 7, 598-604. https://doi.org/10.1186/bcr1200
  2. Balkwill F, Mantovani A (2001). Inflammation and cancer: back to Virchow? Lancet, 357, 539-45. https://doi.org/10.1016/S0140-6736(00)04046-0
  3. Biswas DK, Cruz AP, Gansberger E, Pardee AB (2000). Epidermal growth factor-induced nuclear factor kB activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. PNAS, 97, 8542-47. https://doi.org/10.1073/pnas.97.15.8542
  4. Biswas DK, Dai S-C, Cruz A, et al (2001). The nuclear factor kappa B (NF-kB): A potential therapeutic target for estrogen receptor negative breast cancers. PNAS, 98, 10386-91. https://doi.org/10.1073/pnas.151257998
  5. Biswas DK, Martin KJ, McAlister C, et al (2003). Apoptosis Caused by Chemotherapeutic Inhibition of Nuclear FactorkappaB Activation. Cancer Res, 63, 290-95.
  6. Borg A, Tandon AH, Sigurdsson H, et al (1990). HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res, 50, 4332-7.
  7. Carter CL, Allen C, Henson D (1989). Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer, 63, 181-7. https://doi.org/10.1002/1097-0142(19890101)63:1<181::AID-CNCR2820630129>3.0.CO;2-H
  8. Chen LF, Greene WC (2004). Shaping the nuclear action of NF-kappaB. Nature Rev, 5, 392-401. https://doi.org/10.1038/nrm1368
  9. Cooke T, Reeves J, Lanigan A, Stanton P (2001). HER2 as a prognostic and predictive marker for breast cancer. Ann Oncol, 12, 23-28.
  10. Ferlay J BF, Pisani P, Parkin DM, (2000). Cancer Incidence, Mortality and Prevalence Worldwide. Globocan, Version 1.0.
  11. Ferlay J SH, Bray F, Forman D, Mathers C and Parkin DM (2008). Cancer Incidence and Mortality Worldwide. Globocan, Version 1.2
  12. Greten FR, Karin M (2004). The IKK/NF-${\kappa}B$ activation pathway-a target for prevention. Cancer Letters, 206, 193-99. https://doi.org/10.1016/j.canlet.2003.08.029
  13. Gupta SC, Sundaram C, Reuter S, Bharat B (2010). Aggarwal. Inhibiting NF-${\kappa}B$ activation by small molecules as a therapeutic strategy. Biochimica et Biophysica Acta, 1799, 775-87. https://doi.org/10.1016/j.bbagrm.2010.05.004
  14. Henson DE, Ries L, Freedman LS, et al (1991). Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. Cancer, 68, 2142-49. https://doi.org/10.1002/1097-0142(19911115)68:10<2142::AID-CNCR2820681010>3.0.CO;2-D
  15. Houa M-F, Lin S-B, Yu SS, et al (2003). The clinical significance between activation of nuclear factor kappa B transcription factor and overexpression of HER-2/neu oncoprotein in Taiwanese patients with breast cancer. Clin Chim Acta, 334, 137-144. https://doi.org/10.1016/S0009-8981(03)00196-7
  16. Jana D, Sarkar DK, Maji A, et al (2012). Can cyclo-oxygenase-2 be a useful prognostic and risk stratification marker in breast cancer? J Indian Med Assoc, 110, 429-33.
  17. Merkhofer EC, Cogswell P, Baldwin AS (2010). Her2 activates NF-${\kappa}B$ and induces invasion through the canonical pathway involving IKK${\alpha}$. Oncogene, 29, 1238-48. https://doi.org/10.1038/onc.2009.410
  18. Nakshatri H, Bhat-Nakshatri P, Martin DA, et al (1997). Constitutive activation of NF-kB during progression of breast cancer to hormone-independent growth. Molecul Cell Biol, 17, 3629-39. https://doi.org/10.1128/MCB.17.7.3629
  19. Yamashita H, Nishio M, Toyama T, et al (2004). Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res, 6, 24-30. https://doi.org/10.1186/bcr843
  20. Kalkhoven E, Wissink S, van der Saag PT, van der Burg B (1996). A role for transcription factor NF-${\kappa}B$ in autoimmunity: possible interactions of genes, sex, and the immune response. J Biol Chem , 271, 6217-24. https://doi.org/10.1074/jbc.271.11.6217
  21. Karin M, Lin A (2002). NF-kappaB at the crossroads of life and death. Nat Immunol, 3, 221-27.
  22. Montagut C, Tusquets I, Ferrer B, et al (2006), Activation of nuclear factor-${\kappa}B$ is linked to resistance to neoadjuvant chemotherapy in breast cancer patients. Endocrine-Related Cancer, 13, 607-16. https://doi.org/10.1677/erc.1.01171
  23. Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ Jr and Sledge GW Jr (1997).Constitutive activation of NFkappaB during progression of breast cancer to hormone-independent growth. Molecular and Cellular Biology, 17, 3629-39. https://doi.org/10.1128/MCB.17.7.3629
  24. Radhakrishnan SK, Kamalakaran S (2006). Pro-apoptotic role of NF-${\kappa}B$: Implications for cancer therapy. Biochim Biophys Acta, 1766, 53-62.
  25. Sarkar DK, Lahiri S, Pandey S (2009). Is estrogen receptor study useful in prognostication of breast cancer patients in India? Indian J Surg Oncol, 1, 37-9.
  26. Sen U, Sankaranarayanan R, Mandal S, et al (2002). Cancer patterns in eastern India: The first report of the Kolkata Cancer Registry. Int J Cancer, 100, 86-91. https://doi.org/10.1002/ijc.10446
  27. Sethi G, Sung B, and Aggarwal BB (2008). Nuclear Factor-${\kappa}B$ activation: From bench to bedside, Exp Biol Med, 233, 21-31. https://doi.org/10.3181/0707-MR-196
  28. Sethi G, Tergaonkar V (2009). Potential pharmacological control of the NF-kB pathway. Cell, 30, 313-21
  29. Taneja P, Maglic D, Kai F, et al (2010). Classical and novel prognostic markers for breast cancer and their clinical significance. Oncology, 4, 15-34.
  30. Tovey SM, Brown S, Doughty JC, et al (2009). Poor survival outcomes in HER2-positive breast cancer patients with lowgrade, node-negative tumors. Br J Cancer, 100, 680 - 83. https://doi.org/10.1038/sj.bjc.6604940
  31. Van Laere SJ, Van der Auwera I, Van den Eynden GG, et al (2007). NF-kB activation in inflammatory breast cancer is associated with oestrogen receptor downregulation, secondary to EGFR and/or ErbB2 overexpression and MAPK hyperactivation. Br J Cancer, 97, 659-69. https://doi.org/10.1038/sj.bjc.6603906
  32. Wu JT, Kral JG (2005). The NF-${\kappa}B$/I${\kappa}B$ signaling system: A molecular target in breast cancer therapy. J Surgical Res, 123, 158-69 https://doi.org/10.1016/j.jss.2004.06.006
  33. Wulfing P, Borchard J, Buerger H, et al (2006). HER2-positive circulating tumor cells indicate poor clinical outcome in Stage I to III breast cancer patients. Clin Cancer Res, 12, 1715-20. https://doi.org/10.1158/1078-0432.CCR-05-2087
  34. Zhou Y, Eppenberger-Castori S, Eppenberger U, Benz CC (2005). The NF-${\kappa}B$ pathway and endocrine-resistant breast cancer. Endocrine-Related Cancer, 12, 37-46. https://doi.org/10.1677/erc.1.00977
  35. Zhou Y, Eppenberger-Castori S, Marx C, et al (2005). Activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) identifies a high-risk subset of hormone-dependent breast cancers. Int J Biochem Cell Biol, 37, 1130-44. https://doi.org/10.1016/j.biocel.2004.09.006

Cited by

  1. Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells vol.12, pp.1, 2012, https://doi.org/10.3892/mmr.2015.3411
  2. Effect of Bcl-2 on Apoptosis and Transcription Factor NF-κB Activation Induced by Adriamycin in Bladder Carcinoma BIU87 Cells vol.14, pp.4, 2013, https://doi.org/10.7314/APJCP.2013.14.4.2387
  3. Suppression of inflammatory cascade is implicated in methyl amooranin-mediated inhibition of experimental mammary carcinogenesis pp.08991987, 2013, https://doi.org/10.1002/mc.22067
  4. Garcinol, an Acetyltransferase Inhibitor, Suppresses Proliferation of Breast Cancer Cell Line MCF-7 Promoted by 17β-Estradiol vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.5001
  5. Effect of Lymphangiogenesis and Lymphovascular Invasion on the Survival Pattern of Breast Cancer Patients vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6287
  6. Role of Cyclooxygenase 2 (COX-2) in Prognosis of Breast Cancer vol.5, pp.1, 2014, https://doi.org/10.1007/s13193-014-0290-y
  7. Can Molecular Subtyping Replace Axillary Nodal Status as Prognostic Marker in Breast Cancer? vol.5, pp.4, 2014, https://doi.org/10.1007/s13193-014-0309-4
  8. Trianthema portulacastrum Linn. Displays Anti-Inflammatory Responses during Chemically Induced Rat Mammary Tumorigenesis through Simultaneous and Differential Regulation of NF-κB and Nrf2 Signaling Pathways vol.16, pp.2, 2015, https://doi.org/10.3390/ijms16022426