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Citations to this article

Increased NOS2 predicts poor survival in estrogen receptor–negative breast cancer patients
Sharon A. Glynn, … , Robert M. Stephens, Stefan Ambs
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.
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Research Article Oncology Article has an altmetric score of 3

Increased NOS2 predicts poor survival in estrogen receptor–negative breast cancer patients

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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

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 Total
Citations: 6 12 14 10 8 9 4 5 8 12 15 8 11 16 5 1 144
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Citations to this article in year 2016 (12)

Title and authors Publication Year
T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells
I Marigo, S Zilio, G Desantis, B Mlecnik, AH Agnellini, S Ugel, MS Sasso, JE Qualls, F Kratochvill, P Zanovello, B Molon, CH Ries, V Runza, S Hoves, AM Bilocq, G Bindea, EM Mazza, S Bicciato, J Galon, PJ Murray, V Bronte
Cancer Cell 2016
Metabolic, autophagic, and mitophagic activities in cancer initiation and progression
A Hjelmeland, J Zhang
Biomedical journal 2016
Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells
A Kumar, M Ehrenshaft, EJ Tokar, RP Mason, BK Sinha
Biochimica et Biophysica Acta (BBA) - General Subjects 2016
Inducible Nitric Oxide Synthase (NOS2) in the Carcinogenesis of Gastrointestinal Cancers
GA de Oliveira, R Cheng, LA Ridnour, D Basudhar, V Somasundaram, DW McVicar, HP Monteiro, DA Wink
Antioxidants & Redox Signaling 2016
Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis
L Martinez, E Thames, J Kim, G Chaudhuri, R Singh, S Pervin
BMC Cancer 2016
Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFκB and nitric oxide pathways
HE Hasasna, A Saleh, HA Samri, K Athamneh, S Attoub, K Arafat, N Benhalilou, S Alyan, J Viallet, YA Dhaheri, A Eid, R Iratni
Scientific Reports 2016
Chemoproteomic Strategy to Quantitatively Monitor Transnitrosation Uncovers Functionally Relevant S-Nitrosation Sites on Cathepsin D and HADH2
Y Zhou, SL Wynia-Smith, SM Couvertier, KS Kalous, MA Marletta, BC Smith, E Weerapana
Cell Chemical Biology 2016
Nitric Oxide Synthase-2-Derived Nitric Oxide Drives Multiple Pathways of Breast Cancer Progression
D Basudhar, V Somasundaram, GA de Oliveira, A Kesarwala, JL Heinecke, RY Cheng, SA Glynn, S Ambs, DA Wink, LA Ridnour
Antioxidants & Redox Signaling 2016
Thiol-Activated HNO Release from a Ruthenium Antiangiogenesis Complex and HIF-1α Inhibition for Cancer Therapy
EH Sousa, LA Ridnour, FS Gouveia, CD da Silva, DA Wink, LG de Lopes, PJ Sadler
ACS chemical biology 2016
Role of RPL39 in Metaplastic Breast Cancer
B Dave, DD Gonzalez, ZB Liu, X Li, H Wong, S Granados, NE Ezzedine, DH Sieglaff, JE Ensor, KD Miller, M Radovich, A KarinaEtrovic, SS Gross, O Elemento, GB Mills, MZ Gilcrease, JC Chang
JNCI Journal of the National Cancer Institute 2016
Review of Triple Negative Breast Cancer and the Impact of Inducible Nitric Oxide Synthase on Tumor Biology and Patient Outcomes
EM Walsh, MM Keane, DA Wink, G Callagy, SA Glynn
Critical Reviews in Oncogenesis 2016
Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective
BK Sinha
Journal of cancer science & therapy 2016

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