In this study, we examined the unique relationship of
maspin, a
serine protease inhibitor (
serpin), that plays a critical role in mammary gland development and is silenced during
breast cancer progression, and
nitric oxide (NO), a multifaceted water and
lipid soluble
free radical. The hypothesis tested was that there is a correlation between
endothelial nitric oxide synthase and
maspin in MCF-7 cells and that NO is capable of regulating
maspin expression. An experimental system was developed in which cellular levels of NO in normal human mammary epithelial cells and the
breast cancer cell line MCF-7 could be altered using NO modulators. The effect(s) of NO modulators on
maspin was measured using
reverse transcriptase-polymerase chain reaction and Western blot analysis of subcellular fractions of both cell types. The data revealed that NO induced
maspin expression in MCF-7 cells, and the induced
maspin resulted in diminished cell motility and invasion, concomitant with an increase in the apoptotic index. This novel finding provides new information regarding the molecular role of
maspin in regulating mammary epithelial growth, remodeling,
tumor progression, and the metastatic process. More significantly, these findings could have a potential impact on future therapeutic intervention strategies for
breast cancer. Targeted delivery of NO within the tumor microenvironment could provide a feasible noninvasive approach for effective treatment.