Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor invasion and progression. MMP-9 is a member of the MMP family and is also known as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic activity against type IV collagen, a major component of the basement membrane. Our study aims to examine the association of Gelatinase B (-1562C > T) promoter polymorphism with breast cancer invasion and progression. The study involves 200 breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T (rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase chain reaction and gel electrophoresis. The genotypes were determined and compared between patients and controls, and the influence of the polymorphism on clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9 polymorphism was detected more frequently in breast cancer patients than controls (p < 0.001). Our results suggest the clinical importance of MMP-9 gene polymorphism (-1562C > T) in breast cancer patients. The study may also help in identifying individuals at risk of developing breast cancer.
Breast cancer (BC) is the most common form of carcinoma and a primary cause of morbidity and mortality globally. Oxidative stress represents as an important factor in carcinogenesis and may play a role in initiation and progression of tumors. Oxidative stress-induced NO• damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. It is caused by an unfavorable balance between reactive oxygen species/reactive nitrogen species (ROS/RNS) and antioxidant defenses. ROS/RNS are generated during normal cellular metabolism, as a result of the influence of various environmental factors, as well as during pathological processes.Nitric oxide (NO•) is a ubiquitous, short-lived free radical produced from L-arginine by nitric oxide synthases (NOSs), and isoforms of NOS exist, depending on the site of origin: endothelial (eNOS), neuronal (nNOS), mitochondrial (mtNOS), and inducible (iNOS). eNOS is responsible for the endothelial synthesis of NO• and has shown to modulate cancer-related events such as inflammation, angiogenesis, apoptosis, cell cycle, invasion, and metastasis. Genetic studies also showed that eNOS gene polymorphisms are associated with the development of breast cancer. Therefore, selective targeting of eNOS may prove a potential strategy for prevention and treatment of breast cancer.
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