Neutrophil Elastase Inhibitor Elafin Triggers Rb-Mediated wth Arrest and Caspase-Dependent Apoptosis
نویسندگان
چکیده
Downlo in, an endogenous inhibitor of neutrophil elastase, is expressed in human mammary epithelial cells but scriptionally downregulated in breast cancer cells. We hypothesized that elafin may exert a tumorssive activity in the context of breast cancer. In this study, we show that the retinoblastoma (Rb) pathoverns the antitumor properties of elafin. In breast cancer cells with functional Rb, the expression of triggered Rb-dependent cell cycle arrest. Elafin also exhibited suppressive activity in breast cancer cell acking Rb, but this was associated with an induction of caspase-3–dependent, p53-independent apocell death. Normal mammary epithelial cells were not affected by elafin. Collectively, these results argue lafin mediates tumor-suppressive effects that are cytostatic or cytotoxic depending on the Rb status. that e Our findings suggest that elafin could be engineered as a therapeutic modality to treat breast cancer without toxicity to normal proliferating cells. Cancer Res; 70(18); 7125–36. ©2010 AACR.
منابع مشابه
In vivo adenovirus-mediated expression of human pre-elafin, a potent neutrophil elastase inhibitor.
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