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BMC Cancer

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Open Access 01-12-2005 | Research article

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

Authors: Weiguo Zhang, Heidi Y Shi, Ming Zhang

Published in: BMC Cancer | Issue 1/2005

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/5/50/prepub

Title: Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins
Authors: Weiguo Zhang
Heidi Y Shi
Ming Zhang
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2005
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-5-50

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