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

Kelly K. Hunt, Hannah Wingate, Tomoya Yokota, Yanna Liu, Gordon Mills, Fan Zhang, Bingliang Fang, Chun Hui Su, Ming Zhang, Min Yi, Khandan Keyomarsi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Introduction: 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.Conclusion: 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.

Original languageEnglish (US)
Article numberR3
JournalBreast Cancer Research
Volume15
Issue number1
DOIs
StatePublished - Jan 15 2013
Externally publishedYes

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Elafin
Pancreatic Elastase
Breast Neoplasms
Heterografts
Growth
Breast
Epithelial Cells
Gene Expression
Neoplasms
Survival
Tumor Burden
Nude Mice
Small Interfering RNA
Cell Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hunt, K. K., Wingate, H., Yokota, T., Liu, Y., Mills, G., Zhang, F., ... Keyomarsi, K. (2013). Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer. Breast Cancer Research, 15(1), [R3]. https://doi.org/10.1186/bcr3374

Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer. / Hunt, Kelly K.; Wingate, Hannah; Yokota, Tomoya; Liu, Yanna; Mills, Gordon; Zhang, Fan; Fang, Bingliang; Su, Chun Hui; Zhang, Ming; Yi, Min; Keyomarsi, Khandan.

In: Breast Cancer Research, Vol. 15, No. 1, R3, 15.01.2013.

Research output: Contribution to journalArticle

Hunt, KK, Wingate, H, Yokota, T, Liu, Y, Mills, G, Zhang, F, Fang, B, Su, CH, Zhang, M, Yi, M & Keyomarsi, K 2013, 'Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer', Breast Cancer Research, vol. 15, no. 1, R3. https://doi.org/10.1186/bcr3374
Hunt, Kelly K. ; Wingate, Hannah ; Yokota, Tomoya ; Liu, Yanna ; Mills, Gordon ; Zhang, Fan ; Fang, Bingliang ; Su, Chun Hui ; Zhang, Ming ; Yi, Min ; Keyomarsi, Khandan. / Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer. In: Breast Cancer Research. 2013 ; Vol. 15, No. 1.
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AB - Introduction: 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.Conclusion: 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.

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