Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer.

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Switzer, CH; Glynn, SA; Ridnour, LA; Cheng, RY-S; Vitek, MP; Ambs, S; Wink, DA

Published Date

  • November 2011

Published In

Volume / Issue

  • 32 / 11

Start / End Page

  • 644 - 651

PubMed ID

  • 21893353

Pubmed Central ID

  • PMC3380363

Electronic International Standard Serial Number (EISSN)

  • 1873-3735

Digital Object Identifier (DOI)

  • 10.1016/


  • eng

Conference Location

  • England