STAMP alters the growth of transformed and ovarian cancer cells

BMC Cancer

Research Article

Elise C Kohn¹  S Stoney Simons²  John A Blackford²  Yuanzheng He³ 

[1] Molecular Signaling Section, Medical Oncology Branch, NCI, National Institutes of Health, 20892, Bethesda, MD, USA;Steroid Hormones Section, Clinical Endocrinology Branch, NIDDK, National Institutes of Health, 20892-1772, Bethesda, MD, USA;Steroid Hormones Section, Clinical Endocrinology Branch, NIDDK, National Institutes of Health, 20892-1772, Bethesda, MD, USA;Lab of Structural Sciences, Van Andel Institute, 333 Bostwick Avenue, 49503, Grand Rapids, MI, USA;

关键词: Ovarian Cancer;    Glucocorticoid Receptor;    Epithelial Ovarian Cancer;    Ovarian Cancer Cell;    Ovarian Cancer Cell Line;   

DOI  :  10.1186/1471-2407-10-128

 received in 2009-08-27, accepted in 2010-04-07,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSteroid 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 EC50) 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.MethodsThe 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.ResultsHigher 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© He et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.