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Sharon A. Glynn, … , Robert M. Stephens, Stefan Ambs
Published October 18, 2010
Citation Information: J Clin Invest. 2010;120(11):3843-3854. https://doi.org/10.1172/JCI42059.
Citation Information: J Clin Invest. 2010;120(11):3843-3854. https://doi.org/10.1172/JCI42059.
Abstract
Inducible nitric oxide synthase (NOS2) is involved in wound healing, angiogenesis, and carcinogenesis. NOS2 upregulation and increased nitric oxide (NO) production affect the redox state of cells and can induce protein, lipid, and DNA modifications. To investigate whether NOS2 levels influence survival of breast cancer patients, we examined NOS2 expression and its association with tumor markers and survival in 248 breast tumors. In multivariable survival analysis, increased NOS2 predicted inferior survival in women with estrogen receptor α–negative (ER-negative) tumors. Microdissected tumor epithelium from ER-negative tumors with high NOS2 had increased IL-8 and a gene expression signature characteristic of basal-like breast cancer with poor prognosis. In cell culture, NO only induced selected signature genes in ER-negative breast cancer cells. ER transgene expression in ER-negative cells inhibited NO-induced upregulation of the stem cell marker CD44 and other proteins encoded by signature genes, but not of IL-8. Exposure to NO also enhanced cell motility and invasion of ER-negative cells. Last, pathway analysis linked the tumor NOS2 gene signature to c-Myc activation. Thus, NOS2 is associated with a basal-like transcription pattern and poor survival of ER-negative patients.
Authors
Sharon A. Glynn, Brenda J. Boersma, Tiffany H. Dorsey, Ming Yi, Harris G. Yfantis, Lisa A. Ridnour, Damali N. Martin, Christopher H. Switzer, Robert S. Hudson, David A. Wink, Dong H. Lee, Robert M. Stephens, Stefan Ambs
Total citations by year
Citation information
Citations to this article (138)
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Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications
D Vasudevan, JR Hickok, RC Bovee, V Pham, LL Mantell, N Bahroos, P Kanabar, XJ Cao, M Maienschein-Cline, BA Garcia, DD Thomas |
Cancer research | 2015 |
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Nitric Oxide Down-Regulates Topoisomerase I and Induces Camptothecin Resistance in Human Breast MCF-7 Tumor Cells
NK Sharma, A Kumar, A Kumari, EJ Tokar, MP Waalkes, CD Bortner, J Williams, M Ehrenshaft, RP Mason, BK Sinha, D Jourd'heuil |
PloS one | 2015 |
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NOS1 expression by melanoma induces IFN signal dysfunction
Qiuzhen Liu, Sara Tomei, Maria Libera Ascierto, Valeria De Giorgi, Davide Bedognetti, Cuilian Dai, Lorenzo Uccellini, Tara Spivey, Zoltan Pos, Jaime Thomas, Jennifer Reinboth, Daniela Murtas, Qianbing Zhang, Lotfi Chouchane, Geoffrey R Weiss, Craig Slingluff, Peter P Lee, Steven Rosenberg, Harvey Alter, Kaitai Yao, Ena Wang, Francesco Marincola |
Journal of Clinical Investigation | 2014 |
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Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling
B Dave, S Granados-Principal, R Zhu, S Benz, S Rabizadeh, P Soon-Shiong, KD Yu, Z Shao, X Li, M Gilcrease, Z Lai, Y Chen, TH Huang, H Shen, X Liu, M Ferrari, M Zhan, ST Wong, M Kumaraswami, V Mittal, X Chen, SS Gross, JC Chang |
Proceedings of the National Academy of Sciences | 2014 |
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Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression
JL Heinecke, LA Ridnour, RY Cheng, CH Switzer, MM Lizardo, C Khanna, SA Glynn, SP Hussain, HA Young, S Ambs, DA Wink |
Proceedings of the National Academy of Sciences | 2014 |
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Gene expression profiles of NO- and HNO-donor treated breast cancer cells: insights into tumor response and resistance pathways
RY Cheng, D Basudhar, LA Ridnour, JL Heinecke, AH Kesarwala, S Glynn, CH Switzer, S Ambs, KM Miranda, DA Wink |
Nitric Oxide | 2014 |
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Cancer cell metabolism and the modulating effects of nitric oxide
CF Chang, AR Diers, N Hogg |
Free radical biology & medicine | 2014 |
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The Activation of the Sox2 RR2 Pluripotency Transcriptional Reporter in Human Breast Cancer Cell Lines is Dynamic and Labels Cells with Higher Tumorigenic Potential
JM Iglesias, O Leis, EÃ Ruiz, JG Barrie, F Garcia-Garcia, A Aduriz, I Beloqui, S Hernandez-Garcia, MP Lopez-Mato, J Dopazo, A Pandiella, JA Menendez, AG Martin |
Frontiers in Oncology | 2014 |
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Potential Anti-Inflammatory Effects of the Hydrophilic Fraction of Pomegranate (Punica granatum L.) Seed Oil on Breast Cancer Cell Lines
S Costantini, F Rusolo, VD Vito, S Moccia, G Picariello, F Capone, E Guerriero, G Castello, M Volpe |
Molecules (Basel, Switzerland) | 2014 |
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Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice?: HERV-K activation in cancer and impact on tumor biology
RF Downey, FJ Sullivan, F Wang-Johanning, S Ambs, FJ Giles, SA Glynn |
International Journal of Cancer | 2014 |
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Myeloid derived suppressor cells: Targets for therapy
TJ Waldron, JG Quatromoni, TA Karakasheva, S Singhal, AK Rustgi |
OncoImmunology | 2013 |
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Role of Nitric Oxide in the Chemistry and Anticancer Activity of Etoposide (VP-16,213)
BK Sinha, S Bhattacharjee, S Chatterjee, JJ Jiang, AG Motten, A Kumar, MG Espey, RP Mason |
Chemical Research in Toxicology | 2013 |
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Analysis of indoleamine 2-3 dioxygenase (IDO1) expression in breast cancer tissue by immunohistochemistry
H Soliman, B Rawal, J Fulp, JH Lee, A Lopez, MM Bui, F Khalil, S Antonia, HG Yfantis, DH Lee, TH Dorsey, S Ambs |
Cancer Immunology, Immunotherapy | 2013 |
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Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NFκB signaling and reduction of nitric oxide production
YA Dhaheri, S Attoub, K Arafat, S Abuqamar, J Viallet, A Saleh, HA Agha, A Eid, R Iratni |
PloS one | 2013 |
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Macrophage-tumor cell interactions regulate the function of nitric oxide
MA Rahat, B Hemmerlein |
Frontiers in physiology | 2013 |
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WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells
W Jiang, DK Crossman, EH Mitchell, P Sohn, MR Crowley, R Serra |
PloS one | 2013 |
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Household income is associated with the p53 mutation frequency in human breast tumors
AM Starks, DN Martin, TH Dorsey, BJ Boersma, TA Wallace, S Ambs |
PloS one | 2013 |
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FOXL1, a novel candidate tumor suppressor, inhibits tumor aggressiveness and predicts outcome in human pancreatic cancer
G Zhang, P He, J Gaedcke, BM Ghadimi, T Ried, HG Yfantis, DH Lee, N Hanna, HR Alexander, SP Hussain |
Cancer research | 2013 |
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Biological nitric oxide signalling: chemistry and terminology
TA Heinrich, RS da Silva, KM Miranda, CH Switzer, DA Wink, JM Fukuto |
British Journal of Pharmacology | 2013 |
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Nitric Oxide Production Upregulates Wnt/ -Catenin Signaling by Inhibiting Dickkopf-1
Q Du, X Zhang, Q Liu, X Zhang, CE Bartels, DA Geller |
Cancer research | 2013 |
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iNOS: A Potential Therapeutic Target for Malignant Glioma
Jahani-Asl A, Bonni A |
Current molecular medicine | 2013 |
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S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer
CH Switzer, SA Glynn, RY Cheng, LA Ridnour, JE Green, S Ambs, DA Wink |
Molecular cancer research : MCR | 2012 |
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Dithiolethiones Inhibit NF-κB Activity via Covalent Modification in Human Estrogen Receptor–Negative Breast Cancer
CH Switzer, RY Cheng, LA Ridnour, MC Murray, V Tazzari, A Sparatore, PD Soldato, HB Hines, SA Glynn, S Ambs, DA Wink |
Cancer research | 2012 |
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Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism
V Somasundaram, D Basudhar, G Bharadwaj, JH No, LA Ridnour, RY Cheng, M Fujita, DD Thomas, SK Anderson, DW McVicar, DA Wink |
Antioxidants & Redox Signaling | 2012 |
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Immunotherapeutic Potential of Anti-Human Endogenous Retrovirus-K Envelope Protein Antibodies in Targeting Breast Tumors
F Wang-Johanning, K Rycaj, JB Plummer, M Li, B Yin, K Frerich, JG Garza, J Shen, K Lin, P Yan, SA Glynn, TH Dorsey, KK Hunt, S Ambs, GL Johanning |
JNCI Journal of the National Cancer Institute | 2012 |
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Nitric Oxide Synthase and Breast Cancer: Role of TIMP-1 in NO-mediated Akt Activation
LA Ridnour, KM Barasch, AN Windhausen, TH Dorsey, MM Lizardo, HG Yfantis, DH Lee, CH Switzer, RY Cheng, JL Heinecke, E Brueggemann, HB Hines, C Khanna, SA Glynn, S Ambs, DA Wink |
PloS one | 2012 |
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Relationship between Tumor DNA Methylation Status and Patient Characteristics in African-American and European-American Women with Breast Cancer
S Wang, TH Dorsey, A Terunuma, RA Kittles, S Ambs, B Kwabi-Addo |
PloS one | 2012 |
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Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer
CH Switzer, RY Cheng, LA Ridnour, SA Glynn, S Ambs, DA Wink |
Breast Cancer Research | 2012 |
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Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma
N Funamizu, C Hu, C Lacy, A Schetter, G Zhang, P He, J Gaedcke, MB Ghadimi, T Ried, HG Yfantis, DH Lee, J Subleski, T Chan, JM Weiss, TC Back, K Yanaga, N Hanna, HR Alexander, A Maitra, SP Hussain |
International Journal of Cancer | 2012 |
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Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: Implication for breast carcinogenesis
J Weisz, DA Shearer, E Murata, SD Patrick, B Han, A Berg, GA Clawson |
Cancer biology & therapy | 2012 |
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S-Nitrosation Mediates Multiple Pathways That Lead to Tumor Progression in Estrogen Receptor-Negative Breast Cancer
CH Switzer, LA Ridnour, R Cheng, J Heinecke, A Burke, S Glynn, S Ambs, DA Wink |
Forum on immunopathological diseases and therapeutics | 2012 |
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The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms
KV Lu'o'ng, LT Nguyễn |
Cancer management and research | 2012 |
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Redox regulation of epidermal growth factor receptor signaling through cysteine oxidation
TH Truong, KS Carroll |
Biochemistry | 2012 |
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S-nitrosylation of Ras in breast cancer
HE Marshall, MW Foster |
Breast Cancer Research | 2012 |
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Molecular Pathways: Toll-like Receptors in the Tumor Microenvironment--Poor Prognosis or New Therapeutic Opportunity
LA Ridnour, RY Cheng, CH Switzer, JL Heinecke, S Ambs, S Glynn, HA Young, G Trinchieri, DA Wink |
Clinical cancer research | 2012 |
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Part II. Mitochondrial mutational status of high nitric oxide adapted cell line BT-20 (BT-20-HNO) as it relates to human primary breast tumors
HD Vitto, BS Mendonça, KM Elseth, BJ Vesper, EA Portari, CV Gallo, WA Paradise, FD Rumjanek, JA Radosevich |
Tumor Biology | 2012 |
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Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients.
Herrera AC, Panis C, Victorino VJ, Campos FC, Colado-Simão AN, Cecchini AL, Cecchini R |
Cancer Immunology, Immunotherapy | 2012 |
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Interactions among genes, tumor biology and the environment in cancer health disparities: examining the evidence on a national and global scale
TA Wallace, DN Martin, S Ambs |
Carcinogenesis | 2011 |
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Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer
CH Switzer, SA Glynn, LA Ridnour, RY Cheng, MP Vitek, S Ambs, DA Wink |
Trends in Pharmacological Sciences | 2011 |
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Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer
S Ambs, SA Glynn |
Cell cycle (Georgetown, Tex.) | 2011 |
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Nitric oxide suppresses tumor cell migration through N-Myc downstream-regulated gene-1 (NDRG1) expression: role of chelatable iron
JR Hickok, S Sahni, Y Mikhed, MG Bonini, DD Thomas |
The Journal of biological chemistry | 2011 |
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The role of melanoma tumor-derived nitric oxide in the tumor inflammatory microenvironment: its impact on the chemokine expression profile, including suppression of CXCL10
K Tanese, EA Grimm, S Ekmekcioglu |
International Journal of Cancer | 2011 |
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Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
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