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

Hunt KK, Wingate H, Yokota T, Liu Y, Mills GB, Zhang F, Fang B, Su CH, Zhang M, Yi M, Keyomarsi K - Breast Cancer Res. (2013)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

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.

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Elafin is expressed in non-tumorigenic mammary epithelial cells but not breast cancer cells. A) Lysates were collected from a panel of non-tumorigenic breast epithelial cells (mortal and immortal) and breast cancer cells (ER-positive and ER-negative) and subjected to Western blot analysis to detect elafin expression. B) Elafin levels were also assessed after treatment with PBS, Adenoviral luciferase (Luc), or elafin. Actin expression was assessed as a loading control. C) Breast cancer cell lines (MDA-MB-436, MDA-MB-157, MDA-MB-231 and MDA-MB-468) and non-tumorigenic breast epithelial cells (76NE6 and MCF-10A) were treated with PBS, luciferase (Luc) or elafin, cultured and counted for each day for four days.
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Figure 4: Elafin is expressed in non-tumorigenic mammary epithelial cells but not breast cancer cells. A) Lysates were collected from a panel of non-tumorigenic breast epithelial cells (mortal and immortal) and breast cancer cells (ER-positive and ER-negative) and subjected to Western blot analysis to detect elafin expression. B) Elafin levels were also assessed after treatment with PBS, Adenoviral luciferase (Luc), or elafin. Actin expression was assessed as a loading control. C) Breast cancer cell lines (MDA-MB-436, MDA-MB-157, MDA-MB-231 and MDA-MB-468) and non-tumorigenic breast epithelial cells (76NE6 and MCF-10A) were treated with PBS, luciferase (Luc) or elafin, cultured and counted for each day for four days.

Mentions: Elafin expression differs at the level of transcription between normal mammary epithelial cells and breast carcinoma cells [7,24]. Our data (Figure 3) suggested that tumor cells lack expression of the elafin protein and that a decrease in elafin is associated with increased elastase expression and activity. To further investigate whether the differences between normal and tumor cells persist after translation, we evaluated elafin protein expression in mammary epithelial and breast carcinoma cells. Elafin protein was expressed in all of the non-tumorigenic breast epithelial cells, mortal or immortal (Figure 4A). In contrast, elafin protein was not expressed in any of the breast carcinoma cell lines, whether positive for ER or not (Figure 4A), suggesting that elafin is differentially expressed at the protein level between normal and tumor cells.


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

Hunt KK, Wingate H, Yokota T, Liu Y, Mills GB, Zhang F, Fang B, Su CH, Zhang M, Yi M, Keyomarsi K - Breast Cancer Res. (2013)

Elafin is expressed in non-tumorigenic mammary epithelial cells but not breast cancer cells. A) Lysates were collected from a panel of non-tumorigenic breast epithelial cells (mortal and immortal) and breast cancer cells (ER-positive and ER-negative) and subjected to Western blot analysis to detect elafin expression. B) Elafin levels were also assessed after treatment with PBS, Adenoviral luciferase (Luc), or elafin. Actin expression was assessed as a loading control. C) Breast cancer cell lines (MDA-MB-436, MDA-MB-157, MDA-MB-231 and MDA-MB-468) and non-tumorigenic breast epithelial cells (76NE6 and MCF-10A) were treated with PBS, luciferase (Luc) or elafin, cultured and counted for each day for four days.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672770&req=5

Figure 4: Elafin is expressed in non-tumorigenic mammary epithelial cells but not breast cancer cells. A) Lysates were collected from a panel of non-tumorigenic breast epithelial cells (mortal and immortal) and breast cancer cells (ER-positive and ER-negative) and subjected to Western blot analysis to detect elafin expression. B) Elafin levels were also assessed after treatment with PBS, Adenoviral luciferase (Luc), or elafin. Actin expression was assessed as a loading control. C) Breast cancer cell lines (MDA-MB-436, MDA-MB-157, MDA-MB-231 and MDA-MB-468) and non-tumorigenic breast epithelial cells (76NE6 and MCF-10A) were treated with PBS, luciferase (Luc) or elafin, cultured and counted for each day for four days.
Mentions: Elafin expression differs at the level of transcription between normal mammary epithelial cells and breast carcinoma cells [7,24]. Our data (Figure 3) suggested that tumor cells lack expression of the elafin protein and that a decrease in elafin is associated with increased elastase expression and activity. To further investigate whether the differences between normal and tumor cells persist after translation, we evaluated elafin protein expression in mammary epithelial and breast carcinoma cells. Elafin protein was expressed in all of the non-tumorigenic breast epithelial cells, mortal or immortal (Figure 4A). In contrast, elafin protein was not expressed in any of the breast carcinoma cell lines, whether positive for ER or not (Figure 4A), suggesting that elafin is differentially expressed at the protein level between normal and tumor cells.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

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.

Show MeSH
Related in: MedlinePlus