title: Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer.
abstract: Basal-like breast cancer is an aggressive disease with limited therapeutic options because these tumors frequently express the 'triple-negative' phenotype. We have recently reported that inducible nitric oxide synthase (NOS2) is a strong predictor of survival in patients with estrogen receptor negative [ER(-)] breast cancer, and that NOS2 expression is correlated with a basal-like phenotype. Recent reports also describe the pro-tumor effects of NO in breast and many other types of cancer. NO promotes cancer progression by activating several oncogenic signaling pathways such as extracellular signal-regulated kinases (ERK)-1/2, phosphoinositide 3-kinases (PI3K)/Akt, and c-Myc. Protein phosphatase 2A (PP2A) is a tumor suppressor that negatively regulates the same cancer-related signaling pathways that are activated by NO. PP2A activity is suppressed in tumor cells, but potential pharmacological agents have recently been described to increase PP2A activity in ER(-) breast cancer cells. We examine here the various functions of NO and PP2A in breast cancer and propose a novel mechanism by which activation of PP2A antagonizes NO signaling that promotes ER(-) breast cancer.
authors: Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Christopher H
authors: CH
authors: Switzer
authors: Sharon A
authors: SA
authors: Glynn
authors: Lisa A
authors: LA
authors: Ridnour
authors: Robert Y-S
authors: RY
authors: Cheng
authors: Michael P
authors: MP
authors: Vitek
authors: Stefan
authors: S
authors: Ambs
authors: David A
authors: DA
authors: Wink
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D011960:Receptors, Estrogen; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases; D054648:Protein Phosphatase 2