Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer

53Citations
Citations of this article
57Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Inducible nitric oxide synthase (NOS2) is an inflammation responsive enzyme (EC 1.14.13.39) that is induced during acute and chronic inflammation and tissue injury as part of the host defense and wound healing process. NOS2 upregulation leads to increased nitric oxide (NO) production, the means by which this enzyme can initiate NO-dependent signal transduction, influence the redox state of cells and induce modifications of proteins, lipids and DNA. Aberrant expression of NOS2 has been observed in many types of human tumors. In breast cancer, increased NOS2 is associated with markers of poor outcome and decreased survival. Growth factor and cytokine signaling, tissue remodeling, NFκB activation and hypoxia are candidate mechanisms that induce NOS2 in tumor epithelial and tumor-infiltrating cells. NOS2 induction will trigger the release of variable amounts of NO into the tumor microenvironment and can activate oncogenic pathways, including the Akt, epidermal growth factor receptor and c-Myc signaling pathways, and stimulate tumor microvascularization. Constitutively increased NO levels may also select for mutant p53 cells to overcome the tumor suppressor function of NO-activated wild-type p53. More recent findings suggest that NO induces stem cell-like tumor characteristics in breast cancer. In this review, we will discuss the effects of NO in tumor biology and disease progression with an emphasis on breast cancer, and will examine the mechanisms that link increased NO to a basal-like transcription pattern in human breast tumors and poor disease outcome. ©2011 Landes Bioscience.

Cite

CITATION STYLE

APA

Ambs, S., & Glynn, S. A. (2011, February 15). Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer. Cell Cycle. Taylor and Francis Inc. https://doi.org/10.4161/cc.10.4.14864

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free