Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins

<p>Abstract</p> <p>Background</p> <p>Maspin is a member of serpin family with tumor suppressing activity. Recent studies of maspin in animal models strongly support maspin's role as an inhibitor against the growth of primary tumor sand the process of metastasis. Ho...

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Main Authors: Zhang Ming, Shi Heidi Y, Zhang Weiguo
Format: Article
Language:English
Published: BMC 2005-05-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/5/50
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spelling doaj-e6397c1c4bea42fc99d5dfd7b60587f02020-11-24T21:18:33ZengBMCBMC Cancer1471-24072005-05-01515010.1186/1471-2407-5-50Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteinsZhang MingShi Heidi YZhang Weiguo<p>Abstract</p> <p>Background</p> <p>Maspin is a member of serpin family with tumor suppressing activity. Recent studies of maspin in animal models strongly support maspin's role as an inhibitor against the growth of primary tumor sand the process of metastasis. However, the molecular mechanism underlying this inhibition has not been fully elucidated. In this report, we analyze the effect of maspin on tumor cell apoptosis under several stress conditions.</p> <p>Methods</p> <p>Stable clones overexpressing maspin are established in the mouse mammary tumor TM40D cells. They are treated with staurosporine, TNF-alpha, and serum starvation. The rates of cell apoptosis are analyzed by TUNEL assay. Inhibitors against caspase 8 and 9 are used in the apoptosis assay. Western blot analysis and ribonuclease protection assay (RPA) are performed to examine the expression of Bcl2 family genes.</p> <p>Results</p> <p>We report that maspin expressing tumor cells have increased rate of apoptosis when they are treated with staurosporine and serum starvation. The effect is not through extracellular maspin. Maspin-mediated apoptosis is partially blocked by caspase 8 and 9 inhibitors, and is accompanied by changes in the Bcl-2 family proteins. Maspin-expressing tumor cells have a reduced level of anti-apoptotic protein Bcl-2, and an increased level of pro-apoptotic protein Bax. The regulation is not controlled at the transcriptional level but is through selective control of Bcl-2 and Bax protein stability.</p> <p>Conclusion</p> <p>Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl2 family proteins. Such change results in an increased release of cytochrome c from mitochondria, thus the increased apoptosis in maspin-expressing cells. This evidence strongly suggests that the induction of apoptosis in maspin-overexpressing cells represents a major mechanism by which maspin inhibits breast tumor progression.</p> http://www.biomedcentral.com/1471-2407/5/50
collection DOAJ
language English
format Article
sources DOAJ
author Zhang Ming
Shi Heidi Y
Zhang Weiguo
spellingShingle Zhang Ming
Shi Heidi Y
Zhang Weiguo
Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
BMC Cancer
author_facet Zhang Ming
Shi Heidi Y
Zhang Weiguo
author_sort Zhang Ming
title Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
title_short Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
title_full Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
title_fullStr Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
title_full_unstemmed Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
title_sort maspin overexpression modulates tumor cell apoptosis through the regulation of bcl-2 family proteins
publisher BMC
series BMC Cancer
issn 1471-2407
publishDate 2005-05-01
description <p>Abstract</p> <p>Background</p> <p>Maspin is a member of serpin family with tumor suppressing activity. Recent studies of maspin in animal models strongly support maspin's role as an inhibitor against the growth of primary tumor sand the process of metastasis. However, the molecular mechanism underlying this inhibition has not been fully elucidated. In this report, we analyze the effect of maspin on tumor cell apoptosis under several stress conditions.</p> <p>Methods</p> <p>Stable clones overexpressing maspin are established in the mouse mammary tumor TM40D cells. They are treated with staurosporine, TNF-alpha, and serum starvation. The rates of cell apoptosis are analyzed by TUNEL assay. Inhibitors against caspase 8 and 9 are used in the apoptosis assay. Western blot analysis and ribonuclease protection assay (RPA) are performed to examine the expression of Bcl2 family genes.</p> <p>Results</p> <p>We report that maspin expressing tumor cells have increased rate of apoptosis when they are treated with staurosporine and serum starvation. The effect is not through extracellular maspin. Maspin-mediated apoptosis is partially blocked by caspase 8 and 9 inhibitors, and is accompanied by changes in the Bcl-2 family proteins. Maspin-expressing tumor cells have a reduced level of anti-apoptotic protein Bcl-2, and an increased level of pro-apoptotic protein Bax. The regulation is not controlled at the transcriptional level but is through selective control of Bcl-2 and Bax protein stability.</p> <p>Conclusion</p> <p>Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl2 family proteins. Such change results in an increased release of cytochrome c from mitochondria, thus the increased apoptosis in maspin-expressing cells. This evidence strongly suggests that the induction of apoptosis in maspin-overexpressing cells represents a major mechanism by which maspin inhibits breast tumor progression.</p>
url http://www.biomedcentral.com/1471-2407/5/50
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AT shiheidiy maspinoverexpressionmodulatestumorcellapoptosisthroughtheregulationofbcl2familyproteins
AT zhangweiguo maspinoverexpressionmodulatestumorcellapoptosisthroughtheregulationofbcl2familyproteins
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