Skip to main content

Differential Effects of Omega-3 and Omega-6 fatty Acids on Gene Expression in Breast Cancer Cells

Breast Cancer Research and Treatment volume 101, pages 7–16 (2007)Cite this article

Abstract

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (ω-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (ω-3) EFA as anti-oncogenic factors. The ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the ω-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by ω-3 and ω-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic Acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of ω-3 and ω-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with ω-3 and ω-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of ω-3 and ω-6EFAs.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Apantaku LM (2000) Breast cancer diagnosis and screening. Am Fam Physician 62(3):596–602, 605–606

    Google Scholar 

  2. Apantaku LM (2002) Breast-conserving surgery for breast cancer. Am Fam Physician 66(12): 2271–2278

    PubMed  Google Scholar 

  3. Carroll KK (1985) Dietary fat in relation to mammary carcinogenesis. Princess Takamatsu Symp 16:255–263

    PubMed  CAS  Google Scholar 

  4. Enig MG, Munn RJ, Keeney M (1978) Dietary fat and cancer trends–a critique. Fed Proc 37(9):2215–2220

    PubMed  CAS  Google Scholar 

  5. Hilakivi-Clarke L, Olivo SE, Shajahan A, Khan G, Zhu Y, Zwart A, Cho E, Clarke R (2005) Mechanisms mediating the effects of prepubertal (n–3) polyunsaturated fatty acid diet on breast cancer risk in rats. J Nutr 135(12 Suppl):2946S–2952S

    PubMed  CAS  Google Scholar 

  6. Schley PD, Jijon HB, Robinson LE, Field CJ (2005) Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 92(2):187–195

    Article  PubMed  CAS  Google Scholar 

  7. Wu M, Harvey KA, Ruzmetov N, Welch ZR, Sech L, Jackson K, Stillwell W, Zaloga GP, Siddiqui RA (2005) Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer 117(3):340–348

    Article  PubMed  CAS  Google Scholar 

  8. Cohen LA (1997) Breast cancer risk in rats fed a diet high in n–6 polyunsaturated fatty acids during pregnancy. J Natl Cancer Inst 89(9):662–663

    Article  PubMed  CAS  Google Scholar 

  9. Lanson M, Bougnoux P, Besson P, Lansac J, Hubert B, Couet C, Le Floch O (1990) N–6 polyunsaturated fatty acids in human breast carcinoma phosphatidylethanolamine and early relapse. Br J Cancer 61(5):776–778

    PubMed  CAS  Google Scholar 

  10. Chajes V, Sattler W, Stranzl A, Kostner GM (1995) Influence of n–3 fatty acids on the growth of human breast cancer cells in vitro: relationship to peroxides and vitamin-E. Breast Cancer Res Treat 34(3):199–212

    Article  PubMed  CAS  Google Scholar 

  11. Karmali RA (1989) n–3 fatty acids and cancer. J Intern Med Suppl 731:197–200

    PubMed  CAS  Google Scholar 

  12. Grammatikos SI, Subbaiah PV, Victor TA, Miller WM (1994) n–3 and n–6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines. Br J Cancer 70(2):219–227

    PubMed  CAS  Google Scholar 

  13. Hammamieh R, Chakraborty N, Das R, Jett M (2004) Molecular impacts of antisense complementary to the liver fatty acid binding protein (FABP) mRNA in DU 145 prostate cancer cells in vitro. J Exp Ther Oncol 4(3):195–202

    PubMed  CAS  Google Scholar 

  14. Esmon CT (2003) The protein C pathway. Chest 124(3 Suppl):26S–32S

    Article  PubMed  CAS  Google Scholar 

  15. Yin Y, Liu YX, Jin YJ, Hall EJ, Barrett JC (2003) PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression. Nature 422(6931): 527–531

    Article  PubMed  CAS  Google Scholar 

  16. Germani A, Prabel A, Mourah S, Podgorniak MP, Di Carlo A, Ehrlich R, Gisselbrecht S, Varin-Blank N, Calvo F, Bruzzoni-Giovanelli H (2003) SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway. Oncogene 22(55):8845–8851

    Article  PubMed  CAS  Google Scholar 

  17. Chiyo M, Shimozato O, Yu L, Kawamura K, Iizasa T, Fujisawa T, Tagawa M (2005) Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals. Int J Cancer 115(3):437–442

    Article  PubMed  CAS  Google Scholar 

  18. Zhang Y, Pasparakis M, Kollias G, Simons M (1999) Myocyte-dependent regulation of endothelial cell syndecan-4 expression. Role of TNF-alpha. J Biol Chem 274(21):14,786–14,790

    Article  CAS  Google Scholar 

  19. Lee BP, Rushlow WJ, Chakraborty C, Lala PK (2001) Differential gene expression in premalignant human trophoblast: role of IGFBP-5. Int J Cancer 94(5):674–684

    Article  PubMed  CAS  Google Scholar 

  20. Jensen LE, Whitehead AS (2003) Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis. Cell Signal 15(8):793–802

    PubMed  CAS  Google Scholar 

  21. Nagahata T, Sato T, Tomura A, Onda M, Nishikawa K, Emi M (2005) Identification of RAI3 as a therapeutic target for breast cancer. Endocr Relat Cancer 12(1):65–73

    Article  PubMed  CAS  Google Scholar 

  22. Pigott DA, Grimaldi MA, Dell’Aquila ML, Gaffney EV (1982) Growth inhibitors in plasma derived human serum. In Vitro 18(7):617–625

    PubMed  CAS  Google Scholar 

  23. Cardoso F, Ross JS, Picart MJ, Sotiriou C, Durbecq V (2004) Targeting the ubiquitin-proteasome pathway in breast cancer. Clin Breast Cancer 5(2):148–157

    Article  PubMed  CAS  Google Scholar 

  24. Cloitre M, Heimberg RG, Holt CS, Liebowitz MR (1992) Reaction time to threat stimuli in panic disorder and social phobia. Behav Res Ther 30(6):609–617

    Article  PubMed  CAS  Google Scholar 

  25. Dennis JW, Laferte S, Yagel S, Breitman ML (1989) Asparagine-linked oligosaccharides associated with metastatic cancer. Cancer Cells 1(3):87–92

    PubMed  CAS  Google Scholar 

  26. Xiang Q, Fan SQ, Li J, Tan C, Xiang JJ, Zhang QH, Wang R, Li GY (2002) [Expression of connexin43 and connexin45 in nasopharyngeal carcinoma]. Ai Zheng 21(6):593–596

    PubMed  Google Scholar 

  27. Hodgson JG, Malek T, Bornstein S, Hariono S, Ginzinger DG, Muller WJ, Gray JW (2005) Copy number aberrations in mouse breast tumors reveal loci and genes important in tumorigenic receptor tyrosine kinase signaling. Cancer Res 65(21):9695–9704

    Article  PubMed  CAS  Google Scholar 

  28. Yokozaki H, Budillon A, Tortora G, Meissner S, Beaucage SL, Miki K, Cho-Chung YS (1993) An antisense oligodeoxynucleotide that depletes RI alpha subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells. Cancer Res 53(4):868–872

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work is partially funded by a grant from the US Army Medical Research and Materiel Command, award number DAMD-17-01-1-0268

Author information

Authors and Affiliations

  1. Division of Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, MD, 20910, USA

    Rasha Hammamieh, Nabarun Chakraborty, Stacy-Ann Miller, Edward Waddy, Mohsen Barmada, Rina Das & Marti Jett

  2. Division of Retrovirology, Walter Reed Army Institute of Research, 1600 East Gude Dr., Rockville, MD, 20850, USA

    Sheila A. Peel

  3. Microbiology Department, Howard University College of Medicine, 2400 Sixth Street, Washington, DC, NW, 20059, USA

    Agnes A. Day

Authors
  1. Rasha Hammamieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nabarun Chakraborty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stacy-Ann Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edward Waddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohsen Barmada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rina Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sheila A. Peel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Agnes A. Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marti Jett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marti Jett.

Additional information

R. Hammamieh and N. Chakraborty contributed equally to this manuscript

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hammamieh, R., Chakraborty, N., Miller, SA. et al. Differential Effects of Omega-3 and Omega-6 fatty Acids on Gene Expression in Breast Cancer Cells. Breast Cancer Res Treat 101, 7–16 (2007). https://doi.org/10.1007/s10549-006-9269-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9269-x

Keywords

  • Arachidonic acid (AA)
  • Eicosapentaenoic acid (EPA)
  • DNA microarray
  • N-3 polyunsaturated fatty acid
  • N-6 polyunsaturated fatty acid