NO to breast: when, why and why not?
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.
Division of Endocrinology and Metabolism at Charles Drew University of Medicine and Science, Los Angeles, California 90059, USA. shehlapervin@cdrewu.edu
Shehla
S
Pervin
Gautam
G
Chaudhuri
Rajan
R
Singh
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D018450:Disease Progression; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase