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Nitric oxide synthase activity in human breast cancer
L L Thomsen1, D W Miles, L Happerfield
1Wellcome Research Laboratories, Beckenham, Kent, UK.
British Journal of Cancer
|July 1, 1995
Summary
Nitric oxide synthase (NOS) is present in human breast tumors, with higher activity in invasive cancers. Its expression correlates with tumor grade, suggesting a role in breast cancer progression.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Nitric oxide (NO) is produced by NO synthases (NOS) in various mammalian cells.
- Previous research indicated NOS expression in human gynecological cancers.
- The role of NOS in breast cancer development and progression requires further investigation.
Purpose of the Study:
- To assess the activity and distribution of NO synthases in human breast tumors and normal breast tissue.
- To investigate the correlation between NO synthase activity/expression and breast tumor characteristics, including grade.
Main Methods:
- Enzyme activity assays to measure calcium-dependent (constitutive) and calcium-independent (inducible) NOS activity.
- Measurement of NO biosynthesis levels.
- Immunohistochemical analysis using specific antibodies to detect NOS isoforms and their localization in tumor tissues.
Main Results:
- Both constitutive and inducible NOS activity, along with NO biosynthesis, were significantly higher in invasive breast tumors compared to benign or normal breast tissue.
- In invasive ductal carcinomas, NO biosynthesis levels were notably greater in grade III tumors than in grade II tumors.
- Immunohistochemistry revealed inducible NOS predominantly in tumor-associated macrophages, while constitutive NOS was found in vascular endothelial and myoepithelial cells.
Conclusions:
- NO synthase is expressed in human breast tumors.
- The activity and biosynthesis of NO are elevated in invasive breast cancers.
- NOS expression in breast tumors correlates with tumor grade, suggesting its involvement in breast cancer progression.