Abstract
Nitric oxide is a pleiotropic ancestral molecule, which elicits beneficial effect in many physiological settings but is also tenaciously expressed in numerous pathological conditions, particularly breast tumors. Nitric oxide is particularly harmful in adipogenic milieu of the breast, where it initiates and promotes tumorigenesis. Epidemiological studies have associated populations at a greater risk for developing breast cancer, predominantly estrogen receptor positive tumors, to express specific polymorphic forms of endothelial nitric oxide synthase, that produce sustained low levels of nitric oxide. Low sustained nitric oxide generates oxidative stress and inflammatory conditions at susceptible sites in the heterogeneous microenvironment of the breast, where it promotes cancer related events in specific cell types. Inflammatory conditions also stimulate inducible nitric oxide synthase expression, which dependent on the microenvironment, could promote or inhibit mammary tumors. In this review we re-examine the mechanisms by which nitric oxide promotes initiation and progression of breast cancer and address some of the controversies in the field.
Keywords: Breast cancer, oxidative stress, estrogen, angiogenesis, inflammation, nitric oxide, proliferation
Current Pharmaceutical Design
Title: NO to Breast: When, Why and Why Not?
Volume: 16 Issue: 4
Author(s): Shehla Pervin, Gautam Chaudhuri and Rajan Singh
Affiliation:
Keywords: Breast cancer, oxidative stress, estrogen, angiogenesis, inflammation, nitric oxide, proliferation
Abstract: Nitric oxide is a pleiotropic ancestral molecule, which elicits beneficial effect in many physiological settings but is also tenaciously expressed in numerous pathological conditions, particularly breast tumors. Nitric oxide is particularly harmful in adipogenic milieu of the breast, where it initiates and promotes tumorigenesis. Epidemiological studies have associated populations at a greater risk for developing breast cancer, predominantly estrogen receptor positive tumors, to express specific polymorphic forms of endothelial nitric oxide synthase, that produce sustained low levels of nitric oxide. Low sustained nitric oxide generates oxidative stress and inflammatory conditions at susceptible sites in the heterogeneous microenvironment of the breast, where it promotes cancer related events in specific cell types. Inflammatory conditions also stimulate inducible nitric oxide synthase expression, which dependent on the microenvironment, could promote or inhibit mammary tumors. In this review we re-examine the mechanisms by which nitric oxide promotes initiation and progression of breast cancer and address some of the controversies in the field.
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Cite this article as:
Pervin Shehla, Chaudhuri Gautam and Singh Rajan, NO to Breast: When, Why and Why Not?, Current Pharmaceutical Design 2010; 16 (4) . https://dx.doi.org/10.2174/138161210790232130
DOI https://dx.doi.org/10.2174/138161210790232130 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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