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: Christopher H Switzer, Sharon A Glynn, Lisa A Ridnour, Robert Y-S Cheng, Michael P Vitek, Stefan Ambs, David A Wink
• Journal: Trends in pharmacological sciences (Trends Pharmacol Sci) Vol. 32 Issue 11 Pg. 644-51 (Nov 2011) ISSN: 1873-3735 [Electronic] England
• PMID: 21893353 (Publication Type: Journal Article, Review)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Receptors, Estrogen
• Nitric Oxide
• Extracellular Signal-Regulated MAP Kinases
• Protein Phosphatase 2

Topics

• Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Molecular Targeted Therapy (methods)
• Neoplasms (drug therapy, genetics, metabolism, pathology)
• Nitric Oxide (metabolism)
• Protein Phosphatase 2 (metabolism)
• Receptors, Estrogen (physiology)
• Signal Transduction
• Tumor Cells, Cultured