Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer

Abstract

Elafin is an elastase-specific inhibitor with increased transcription in normal mammary epithelial cells compared to mammary carcinoma cells. In this report, we test the hypothesis that inhibition of elastase, through induction of elafin, leads to inhibition of human breast cancer cell viability and, therefore, predicts survival in breast cancer patients. Panels of normal and immortalized breast epithelial cells, along with breast carcinoma cells, were used to examine the impact of adenoviral-mediated elafin expression or shRNA-mediated inhibition of elastase on the growth of cells and xenografts in nude mice. To determine the prognostic significance of decreased elafin in patients with invasive breast cancer, previously published gene array datasets were interrogated. Elafin expression had no effect on non-tumorigenic cells but resulted in marked inhibition of cell growth in breast cancer cell lines. Control-treated xenografts generated a tumor burden that necessitated sacrifice within one month of initial treatment, whereas xenograft-bearing mice treated with Ad-Elafin were alive at eight months with marked reduction in tumor growth. Elastase inhibition mimicked these results, showing decreased tumor cell growth in vitro and in vivo. Low expression of elafin gene correlated with significantly reduced time to relapse, and when combined with high expression of elastase gene was associated with decreased survival in breast cancer patients. Our data suggest that elafin plays a direct role in the suppression of tumors through inhibition of elastase and thus serves as a prognostic indicator for breast cancer patients.

DOI: 10.1186/bcr3374

Extracted Key Phrases

6 Figures and Tables

02004002014201520162017
Citations per Year

234 Citations

Semantic Scholar estimates that this publication has 234 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@inproceedings{Hunt2012ElafinAI, title={Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer}, author={Kelly Hunt and Hannah F. Wingate and Tomoya Yokota and Yan Liu and Gordon B. Mills and Fan Zhang and Bingliang Fang and Chun-Hui Su and Ming Zhang and Min Yi and Khandan Keyomarsi}, booktitle={Breast Cancer Research}, year={2012} }