title: Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Kelly K
authors: KK
authors: Hunt
authors: Hannah
authors: H
authors: Wingate
authors: Tomoya
authors: T
authors: Yokota
authors: Yanna
authors: Y
authors: Liu
authors: Gordon B
authors: GB
authors: Mills
authors: Fan
authors: F
authors: Zhang
authors: Bingliang
authors: B
authors: Fang
authors: Chun-Hui
authors: CH
authors: Su
authors: Ming
authors: M
authors: Zhang
authors: Min
authors: M
authors: Yi
authors: Khandan
authors: K
authors: Keyomarsi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D053492:Elafin / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011379:Prognosis; D011401:Promoter Regions, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D053492:Elafin; D010196:Pancreatic Elastase