TY - JOUR
T1 - Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer
AU - Hunt, Kelly K.
AU - Wingate, Hannah
AU - Yokota, Tomoya
AU - Liu, Yanna
AU - Mills, Gordon B.
AU - Zhang, Fan
AU - Fang, Bingliang
AU - Su, Chun Hui
AU - Zhang, Ming
AU - Yi, Min
AU - Keyomarsi, Khandan
N1 - Funding Information:
We thank Stephanie Deming and Jessica Marino for their thoughtful editing of the manuscript, and Tuyen Bui and Flavio Palalon for technical assistance. This work was supported by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant, (CA016672), and 5R01CA087548-10 (to KK); the Susan G. Komen for the Cure (KG100521 to KKH); the Breast Cancer Research and Prevention Fund; and the Hamill Foundation (both to KKH).
PY - 2013/1/15
Y1 - 2013/1/15
N2 - 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.
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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U2 - 10.1186/bcr3374
DO - 10.1186/bcr3374
M3 - Article
C2 - 23320734
AN - SCOPUS:84872150361
SN - 1465-5411
VL - 15
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - R3
ER -