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Inflammopharmacology
Published in: Inflammopharmacology 4/2018

01-08-2018 | Original Article

Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer

Authors: Brian M. Kennedy, Randall E. Harris

Published in: Inflammopharmacology | Issue 4/2018

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Abstract

We examined the expression of major inflammatory genes, cyclooxygenase-1 and 2 (COX1, COX2) and arachidonate 5-lipoxygenase (ALOX5) in 1090 tumor samples of invasive breast cancer from The Cancer Genome Atlas (TCGA). Mean cyclooxygenase expression (COX1 + COX2) ranked in the upper 99th percentile of all 20,531 genes and surprisingly, the mean expression of COX1 was more than tenfold higher than COX2. Highly significant correlations were observed between COX2 with eight tumor-promoting genes (EGR2, IL6, RGS2, B3GNT5, SGK1, SLC2A3, SFRP1 and ETS2) and between ALOX5 and ten tumor promoter genes (CD33, MYOF1, NLRP1, GAB3, CD4, IFR8, CYTH4, BTK, FGR, CD37). Expression of CYP19A1 (aromatase) was significantly correlated with COX2, but only in tumors positive for ER, PR and HER2. Tumor-promoting genes correlated with the expression of COX1, COX2, and ALOX5 are known to effectively increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the pathogenesis of breast cancer.
Literature
Barbeau DJ, La KT, Kim KS, Kerpedjieva SS, Shurin GV, Tamama K (2014) Early Growth Response-2 signaling mediates immunomodulatory effects of human multipotential stromal cells. Stem Cells Dev 23(2):155–166CrossRefPubMed
Bernemann C, Hülsewig C, Ruckert C, Schäfer S, Blümel L, Hempel G, Götte M, Greve B, Barth PJ, Kiesel L, Liedtke C (2014) Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling. Mol Cancer 13:174CrossRefPubMedPubMedCentral
Busse WW (1998) Leukotrienes and inflammation. Am J Respir Crit Care Med 157(6):5210–5213CrossRef
Busse W, Kraft M (2005) Cysteinyl leukotrienes in allergic inflammation: strategic target for therapy. Chest 127(4):1312–1326PubMed
Chang S-H, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T (2004) Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci USA 101(2):591–596CrossRefPubMed
Chaudhary B, Elkord E (2016) Regulatory T cells in the tumor microenvironment and cancer progression: role and therapeutic targeting. Vaccines (Basel) 4(3):28CrossRef
Cheah MS, Ley TJ, Tronick SR, Robbins KC (1986) FGR proto-oncogene mRNA induced in B lymphocytes by Epstein–Barr virus infection. Nature 319(6050):238–240CrossRefPubMed
Choi J, Gyamfi J, Jang H, Koo JS (2018) The role of tumor-associated macrophage in breast cancer biology. Histol Histopathol 33:133–145PubMed
Chumsri S, Timothy Howes T, Bao T, Sabnis G, Brodie A (2011) Aromatase, aromatase inhibitors, and breast cancer. J Steroid Biochem Mol Biol 125(1–2):13–22CrossRefPubMedPubMedCentral
Du P, Zhang X, Huang CC, Jafari N, Kibbe WA, Hou L, Lin SM (2010) Comparison of beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinform 11:587CrossRef
Eifert C, Wang X, Kokabee L, Kourtidis A, Jain R, Gerdes MJ, Conklin DS (2013) A novel isoform of the B cell tyrosine kinase BTK protects breast cancer cells from apoptosis. Genes Chromosom Cancer 52(10):961–975CrossRefPubMed
Elsberger B, Fullerton R, Zino S, Jordan F, Mitchell TJ, Brunton VG, Mallon EA, Shiels PG, Edwards J (2010) Breast cancer patients’ clinical outcome measures are associated with Src kinase family member expression. Br J Cancer 103:899–909CrossRefPubMedPubMedCentral
Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG, Li MO (2014) The cellular and molecular origin of tumor-associated macrophages. Science 344(6186):921–925CrossRefPubMedPubMedCentral
Goswami S, Sahai E, Wyckoff JB, Cammer M, Cox D, Pixley FJ, Stanley R, Segall JE, Condeelis JS (2005) Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. Cancer Res 65(12):5278–5283CrossRefPubMed
Hallett RM, Dvorkin-Gheva A, Bane A, Hassell JA (2012) A gene signature for predicting outcome in patients with basal-like breast cancer. Sci Rep 2:227CrossRefPubMedPubMedCentral
Harris RE (2007) Cyclooxygenase-2 (COX-2) and the inflammogenesis of cancer. Subcell Biochem 42:93–126CrossRefPubMed
Harris RE, Robertson FM, Abou-Issa HM, Farrar WB, Brueggemeier R (1999) Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer. Med Hypotheses 52(4):291–292CrossRefPubMed
Herschman HR (1994) Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metastasis Rev 13:241–256CrossRefPubMed
Herschman HR (2002) Historical aspects of COX-2. In: Harris RE (ed) COX-2 blockade in cancer prevention and therapy. Humana Press, Totowa, pp 13–32CrossRef
Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ (2006) The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci 103(21):8173–8178CrossRefPubMed
Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A, Brys M (2012) Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol Oncol Res 18(3):721–728CrossRefPubMedPubMedCentral
Kumar G, Patlolla JM, Madka V, Mohammed A, Li Q, Zhang Y, Biddick L, Singh A, Gillaspy A, Lightfoot S, Steele VE, Kopelovich L, Rao CV (2016) Simultaneous targeting of 5-LOX-COX and ODC block NNK-induced lung adenoma progression to adenocarcinoma in A/J mice. Am J Cancer Res 6(5):894–909PubMedPubMedCentral
Kumari N, Dwarakanath BS, Das A, Bhatt AN (2016) Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol 37(9):11553–11572CrossRefPubMed
Kurkjian C, Janakiram NB, Guruswamy S, Rao CV, Ozer H (2007) The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells. J Clin Oncol 25(18):1537
Li B, Dewey CN (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform 23:323CrossRef
Li H, Zhu F, Boardman LA, Wang L, Oi N, Liu K, Li X, Fu Y, Limburg PJ, Bode AM, Dong Z (2015) Aspirin prevents colorectal cancer by normalizing EGFR expression. EBioMedicine 2(5):447–455CrossRefPubMedPubMedCentral
Man YG, Stojadinovic A, Mason J, Avital I, Bilchik A, Bruecher B, Protic M, Nissan A, Izadjoo M, Zhang X, Jewett A (2013) Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories. J Cancer 4(1):84–95CrossRefPubMedPubMedCentral
Marquina G, Waki H, Fernandez LE, Kon K, Carr A, Valiente O, Perez R, Ando S (1996) Gangliosides expressed in human breast cancer. Can Res 56:5165–5171
Martin ME, Milne TA, Bloyer S, Galoian K, Shen W, Gibbs D, Brock HW, Slany R, Hess JL (2003) Dimerization of MLL fusion proteins immortalizes hematopoietic cells. Cancer Cell 4(3):197–207CrossRefPubMed
Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN, Ueno NT (2012) Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res Treat 136(2):331–345CrossRefPubMed
Morishige M, Hashimoto S, Ogawa E, Toda Y, Kotani H, Hirose M, Wei S, Hashimoto A, Yamada A, Yano H, Mazaki Y, Kodama H, Nio Y, Manabe T, Wada H, Kobayashi H, Sabe H (2008) GEP100 links epidermal growth factor receptor signaling to Arf6 activation to induce breast cancer invasion. Nat Cell Biol 10(1):85–92CrossRefPubMed
Narayanan NK, Nargi D, Attur M, Abramson SB, Narayanan BA (2005) Anticancer effects of licofelone (ML-3000) in prostate cancer cells. Anticancer Res 27(4B):2393–2402
Orlando UD, Garona J, Ripoll GV, Maloberti PM, Solano AR, Avagnina A, Gomez DE, Alonso DF, Podestá EJ (2012) The functional interaction between Acyl-CoA synthetase 4, 5-lipoxygenase and cyclooxygenase-2 controls tumor growth: a novel therapeutic target. PLoS One 7(7):e40794CrossRefPubMedPubMedCentral
Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS (2002) Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8(3):289–293CrossRefPubMed
Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752CrossRefPubMed
Philip M, Rowley DA, Schreiber H (2004) Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 14:433–439CrossRefPubMed
Potapenko IO, Lüders T, Russnes HG, Helland Å, Sørlie T, Kristensen VN, Haakensen VD (2015) Glycan-related gene expression signatures in breast cancer subtypes: relation to survival. Mol Oncol 9(4):861–876CrossRefPubMedPubMedCentral
Prenzel N, Zwick E, Leserer M, Ullrich A (2000) Tyrosine kinase signaling in breast cancer: epidermal growth factor receptor-convergence point for signal integration and diversification. Breast Cancer Res 2(3):184–190CrossRefPubMedPubMedCentral
Rao CV, Janakiram NB, Mohammed A (2012) Lipoxygenase and cyclooxygenase pathways and colorectal cancer prevention. Curr Colorectal Cancer Rep 8(4):316–324CrossRefPubMedPubMedCentral
Rasheed S, Barbacid M, Aaronson S, Gardner MB (1982) Origin and biological properties of a new feline sarcoma virus. Virology 117(1):238–244CrossRefPubMed
Rettenmier CW, Roussel MF, Sherr CJ (1988) The colony-stimulating factor 1 (CSF-1) receptor (c-fms proto-oncogene product) and its ligand. J Cell Sci Suppl 9:27–44CrossRefPubMed
Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, Jones T, Jucknischke U, Scheiblich S, Kaluza K, Gorr IH, Walz A, Abiraj K, Cassier PA, Sica A, Gomez-Roca C, de Visser KE, Italiano A, Le Tourneau C, Delord JP, Levitsky H, Blay JY, Rüttinger D (2014) Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 25(6):846–859CrossRefPubMed
Romano M, Claria J (2003) Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy. FASEB J 17(14):1986–1995CrossRefPubMed
Rose DP (1997) Dietary fat, fatty acids and breast cancer. Breast Cancer 5(1):7–16CrossRef
Samuelsson B (1991) Arachidonic acid metabolism: role in inflammation. Z Rheumatol 50(Suppl 1):3–6PubMed
Schrieber H, Rowley DA (1999) Inflammation and cancer. In: Gallin JI, Snyderman R (eds) Inflammation: basic principles and clinical correlates, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, pp 1117–1129
Schwab M, Praml C, Amler LC (1996) Genomic instability in 1p and human malignancies. Genes Chromosom Cancer 16(4):211–229CrossRefPubMed
Smalley MJ, Iravani M, Leao M, Grigoriadis A, Kendrick H, Dexter T, Fenwick K, Regan JL, Britt K, McDonald S, Lord CJ, MacKay A, Ashworth A (2007) Regulator of G-protein signalling 2 mRNA is differentially expressed in mammary epithelial subpopulations and over-expressed in the majority of breast cancers. Breast Cancer Res 9:R85CrossRefPubMedPubMedCentral
Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMed
Su S, Liao J, Liu J, Huang D, He C, Chen F, Yang LB, Wu W, Chen J, Lin L, Zeng Y, Ouyang N, Cui X, Yao H, Su F, Huang J, Lieberman J, Liu Q, Song E (2017) Blocking the recruitment of naïve CD4+ cells reverses immunosuppression in breast cancer. Cell Res 27(4):462–482CrossRef
Sullivan NJ (2011) Interleukin-6 in the breast tumor microenvironment. In: Gunduz M (ed) Breast cancer-focusing tumor microenvironment, stem cells and metastasis. intech, london, pp 165–182
Taki T, Akiyama M, Saito S, Ono R, Taniwaki M, Kato Y, Yuza Y, Eto Y, Hayashi Y (2005) The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complete translocation involving chromosomes 7, 11, 19 and 22. Oncogene 24:5191–5197CrossRefPubMed
Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 342:232–235CrossRef
Veeck J, Niederacher D, An H, Klopocki E, Wiesmann F, Betz B, Galm O, Camara O, Dürst M, Kristiansen G, Huszka C, Knüchel R, Dahl E (2006) Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis. Oncogene 25(24):3479–3488CrossRefPubMed
Virchow R (1858) Reizung and Reizbarkeit. Arch Pathol Anat Klin Med 14:1–63CrossRef
Virchow R (1863) Aetiologie der neoplastischen Geschwulst/Pathogenie der neoplastischen Geschwulste. In: Die Krankhaften Geschwulste. Verlag von August Hirschwald, Berlin, pp 57–101
Wei Y, Huang H, Qiu Z, Li H, Tan J, Ren G, Wang X (2017) NLRP1 overexpression is correlated with the tumorigenesis and proliferation of human breast tumor. Biomed Res Int 2017:4938473PubMedPubMedCentral
Williams CS, DuBois RN (1996) Prostaglandin endoperoxide synthase: why two isoforms? Am Physiol Soc 270:G393–G400
Williams CB, Yeh ES, Soloff AC (2016) Tumor associated macrophages: unwitting accomplices in breast cancer malignancy. npj. Breast Cancer 2:15025PubMed
Wu X, Li Y, Wang J, Wen X, Marcus MT, Daniels G, Zhang DY, Ye F, Wang LH, Du X, Adams S, Singh B, Zavadil J, Lee P, Monaco ME (2013) Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer. PLoS One 8(10):e77060CrossRefPubMedPubMedCentral
Xu D, Dwyer J, Li H, Duan W, Liu J-P (2008) Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc. J Biol Chem 283(35):23567–23580CrossRefPubMedPubMedCentral
Yoda T, Kikuchi K, Miki Y, Onodera Y, Hata S, Takagi K, Nakamura Y, Hirakawa H, Ishida T, Suzuki T, Ohuchi N, Sasano H, McNamara KM (2015) 11β-Prostaglandin F2α, a bioactive metabolite catalyzed by AKR1C3, stimulates prostaglandin F receptor and induces slug expression in breast cancer. Mol Cell Endocrinol 413:236–247CrossRefPubMed
Yu Y-Q, Tao R, Wei J, Xu Q, Liu S-Z, Ju G-Z, Shi J-P, Zhang X, Xie L, Shen Y (2004) No association between the PTGS2/PLA2G4A locus and schizophrenia in a Chinese population. Prostaglandins Leukot Essent Fatty Acids 71:405–408CrossRefPubMed
Metadata
Title
Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer
Authors
Brian M. Kennedy
Randall E. Harris
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 4/2018
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-018-0489-6

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