STAMP alters the growth of transformed and ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Steroid receptors play major roles in the development, differentiation, and homeostasis of normal and malignant tissue. STAMP is a novel coregulator that not only enhances the ability of p160 coactivator family members TIF2 and SRC-1...

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Main Authors: Kohn Elise C, Blackford John A, He Yuanzheng, Simons S Stoney
Format: Article
Language:English
Published: BMC 2010-04-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/10/128
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author Kohn Elise C
Blackford John A
He Yuanzheng
Simons S Stoney
author_facet Kohn Elise C
Blackford John A
He Yuanzheng
Simons S Stoney
author_sort Kohn Elise C
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Steroid receptors play major roles in the development, differentiation, and homeostasis of normal and malignant tissue. STAMP is a novel coregulator that not only enhances the ability of p160 coactivator family members TIF2 and SRC-1 to increase gene induction by many of the classical steroid receptors but also modulates the potency (or EC<sub>50</sub>) of agonists and the partial agonist activity of antisteroids. These modulatory activities of STAMP are not limited to gene induction but are also observed for receptor-mediated gene repression. However, a physiological role for STAMP remains unclear.</p> <p>Methods</p> <p>The growth rate of HEK293 cells stably transfected with STAMP plasmid and overexpressing STAMP protein is found to be decreased. We therefore asked whether different STAMP levels might also contribute to the abnormal growth rates of cancer cells. Panels of different stage human cancers were screened for altered levels of STAMP mRNA. Those cancers with the greatest apparent changes in STAMP mRNA were pursued in cultured cancer cell lines.</p> <p>Results</p> <p>Higher levels of STAMP are shown to have the physiologically relevant function of reducing the growth of HEK293 cells but, unexpectedly, in a steroid-independent manner. STAMP expression was examined in eight human cancer panels. More extensive studies of ovarian cancers suggested the presence of higher levels of STAMP mRNA. Lowering STAMP mRNA levels with siRNAs alters the proliferation of several ovarian cancer tissue culture lines in a cell line-specific manner. This cell line-specific effect of STAMP is not unique and is also seen for the conventional effects of STAMP on glucocorticoid receptor-regulated gene transactivation.</p> <p>Conclusions</p> <p>This study indicates that a physiological function of STAMP in several settings is to modify cell growth rates in a manner that can be independent of steroid hormones. Studies with eleven tissue culture cell lines of ovarian cancer revealed a cell line-dependent effect of reduced STAMP mRNA on cell growth rates. This cell-line dependency is also seen for STAMP effects on glucocorticoid receptor-mediated transactivation. These preliminary findings suggest that further studies of STAMP in ovarian cancer may yield insight into ovarian cancer proliferation and may be useful in the development of biomarker panels.</p>
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spelling doaj.art-4874a6f43e4e495c852f33fcac103f6d2022-12-22T03:09:58ZengBMCBMC Cancer1471-24072010-04-0110112810.1186/1471-2407-10-128STAMP alters the growth of transformed and ovarian cancer cellsKohn Elise CBlackford John AHe YuanzhengSimons S Stoney<p>Abstract</p> <p>Background</p> <p>Steroid receptors play major roles in the development, differentiation, and homeostasis of normal and malignant tissue. STAMP is a novel coregulator that not only enhances the ability of p160 coactivator family members TIF2 and SRC-1 to increase gene induction by many of the classical steroid receptors but also modulates the potency (or EC<sub>50</sub>) of agonists and the partial agonist activity of antisteroids. These modulatory activities of STAMP are not limited to gene induction but are also observed for receptor-mediated gene repression. However, a physiological role for STAMP remains unclear.</p> <p>Methods</p> <p>The growth rate of HEK293 cells stably transfected with STAMP plasmid and overexpressing STAMP protein is found to be decreased. We therefore asked whether different STAMP levels might also contribute to the abnormal growth rates of cancer cells. Panels of different stage human cancers were screened for altered levels of STAMP mRNA. Those cancers with the greatest apparent changes in STAMP mRNA were pursued in cultured cancer cell lines.</p> <p>Results</p> <p>Higher levels of STAMP are shown to have the physiologically relevant function of reducing the growth of HEK293 cells but, unexpectedly, in a steroid-independent manner. STAMP expression was examined in eight human cancer panels. More extensive studies of ovarian cancers suggested the presence of higher levels of STAMP mRNA. Lowering STAMP mRNA levels with siRNAs alters the proliferation of several ovarian cancer tissue culture lines in a cell line-specific manner. This cell line-specific effect of STAMP is not unique and is also seen for the conventional effects of STAMP on glucocorticoid receptor-regulated gene transactivation.</p> <p>Conclusions</p> <p>This study indicates that a physiological function of STAMP in several settings is to modify cell growth rates in a manner that can be independent of steroid hormones. Studies with eleven tissue culture cell lines of ovarian cancer revealed a cell line-dependent effect of reduced STAMP mRNA on cell growth rates. This cell-line dependency is also seen for STAMP effects on glucocorticoid receptor-mediated transactivation. These preliminary findings suggest that further studies of STAMP in ovarian cancer may yield insight into ovarian cancer proliferation and may be useful in the development of biomarker panels.</p>http://www.biomedcentral.com/1471-2407/10/128
spellingShingle Kohn Elise C
Blackford John A
He Yuanzheng
Simons S Stoney
STAMP alters the growth of transformed and ovarian cancer cells
BMC Cancer
title STAMP alters the growth of transformed and ovarian cancer cells
title_full STAMP alters the growth of transformed and ovarian cancer cells
title_fullStr STAMP alters the growth of transformed and ovarian cancer cells
title_full_unstemmed STAMP alters the growth of transformed and ovarian cancer cells
title_short STAMP alters the growth of transformed and ovarian cancer cells
title_sort stamp alters the growth of transformed and ovarian cancer cells
url http://www.biomedcentral.com/1471-2407/10/128
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AT heyuanzheng stampaltersthegrowthoftransformedandovariancancercells
AT simonssstoney stampaltersthegrowthoftransformedandovariancancercells