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Estrogen and the selective estrogen receptor modulator (SERM) protection against cell death in estrogen receptor alpha and beta expressing U2OS cells

Kallio, Anu; Guo, Tao; Lamminen, Elisa; Seppanen, Jani; Kangas, Lauri; Vaananen, H. Kalervo and Härkönen, Pirkko LU (2008) In Molecular and Cellular Endocrinology 289(1-2). p.38-48
Abstract
In the current work, we compared the ability of 17 beta-estradiol (E-2) and the selective estrogen receptor modulators (SERMs), tamoxifen (Tam), raloxifene (Ral) and ospemifene (Osp) to promote the survival of osteoblast-derived cells against etoposide-incluced apoptosis. In order to compare the roles of the two estrogen receptor (ER) isotypes, we created a U2OS human osteosarcoma cell line stably expressing either ERalpha (ER alpha) or ERbeta (ER beta). Transfection with either of the ERs was able to render the U2OS cells sensitive to E-2. We show that E2 opposed etoposide-induced apoptosis and that the effect was mediated via both ER isotypes. The ER isotype selective agonists propyl-pyrazole-triol (PPT) and diarylpropionitrile (DPN) had... (More)
In the current work, we compared the ability of 17 beta-estradiol (E-2) and the selective estrogen receptor modulators (SERMs), tamoxifen (Tam), raloxifene (Ral) and ospemifene (Osp) to promote the survival of osteoblast-derived cells against etoposide-incluced apoptosis. In order to compare the roles of the two estrogen receptor (ER) isotypes, we created a U2OS human osteosarcoma cell line stably expressing either ERalpha (ER alpha) or ERbeta (ER beta). Transfection with either of the ERs was able to render the U2OS cells sensitive to E-2. We show that E2 opposed etoposide-induced apoptosis and that the effect was mediated via both ER isotypes. The ER isotype selective agonists propyl-pyrazole-triol (PPT) and diarylpropionitrile (DPN) had the same effect in U2OS/ER alpha and U20S/ER beta cells, respectively. Osp also opposed apoptosis at least in U2OS/ERa cells. Tam and Ral were not able to protect against etoposide-induced cell death. In order to evaluate the protective effects of E-2 and Osp upon etoposide challenge, we studied the expression of two E-2-regulated, osteoblast-produced cytokines, IL-6 and OPG in E-2 and SERM-treated U2OS/ER alpha and U2OS/ER beta cells. Etoposide strongly increased expression of IL-6 and decreased that of OPG. E-2 opposed IL-6 increase only in U2OS/ER alpha cells and OPG decrease primarily in ER beta cells. Osp opposed the effect of etoposide on OPG primarily in U2OS/ER beta cells but interestingly, it had little effect on IL-6 expression. E2, PPT, DNP and Osp also inhibited etoposide-induced death and cytokine changes in SAOS-2 osteosarcoma cells expressing endogenous ER alpha and ER beta. Collectively, our results suggest that the osteoblast protective anti-apoptotic effects of E-2 are mediated by both ER alpha and ER beta but those of Osp primarily by ER alpha. In addition, E-2 and Osp opposed the etoposide-induced increase of IL-6 and decrease of OPG which changes would increase osteoclastic activity. These anti-resorptive effects of E-2 and Osp upon etoposide challenge differed from each other and they seemed to be differentially mediated in ER(x and ER beta expressing osteoblast-derived U2OS cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IL-6, OPG, estrogen receptor, estradiol, osteoblast, U2OS
in
Molecular and Cellular Endocrinology
volume
289
issue
1-2
pages
38 - 48
publisher
Elsevier
external identifiers
  • wos:000257841700006
  • scopus:45049086100
ISSN
1872-8057
DOI
10.1016/j.mce.2008.03.005
language
English
LU publication?
yes
id
1425cda5-5f45-47aa-acb1-2a8825b60e29 (old id 1253847)
date added to LUP
2008-11-07 14:33:41
date last changed
2017-10-29 03:28:52
@article{1425cda5-5f45-47aa-acb1-2a8825b60e29,
  abstract     = {In the current work, we compared the ability of 17 beta-estradiol (E-2) and the selective estrogen receptor modulators (SERMs), tamoxifen (Tam), raloxifene (Ral) and ospemifene (Osp) to promote the survival of osteoblast-derived cells against etoposide-incluced apoptosis. In order to compare the roles of the two estrogen receptor (ER) isotypes, we created a U2OS human osteosarcoma cell line stably expressing either ERalpha (ER alpha) or ERbeta (ER beta). Transfection with either of the ERs was able to render the U2OS cells sensitive to E-2. We show that E2 opposed etoposide-induced apoptosis and that the effect was mediated via both ER isotypes. The ER isotype selective agonists propyl-pyrazole-triol (PPT) and diarylpropionitrile (DPN) had the same effect in U2OS/ER alpha and U20S/ER beta cells, respectively. Osp also opposed apoptosis at least in U2OS/ERa cells. Tam and Ral were not able to protect against etoposide-induced cell death. In order to evaluate the protective effects of E-2 and Osp upon etoposide challenge, we studied the expression of two E-2-regulated, osteoblast-produced cytokines, IL-6 and OPG in E-2 and SERM-treated U2OS/ER alpha and U2OS/ER beta cells. Etoposide strongly increased expression of IL-6 and decreased that of OPG. E-2 opposed IL-6 increase only in U2OS/ER alpha cells and OPG decrease primarily in ER beta cells. Osp opposed the effect of etoposide on OPG primarily in U2OS/ER beta cells but interestingly, it had little effect on IL-6 expression. E2, PPT, DNP and Osp also inhibited etoposide-induced death and cytokine changes in SAOS-2 osteosarcoma cells expressing endogenous ER alpha and ER beta. Collectively, our results suggest that the osteoblast protective anti-apoptotic effects of E-2 are mediated by both ER alpha and ER beta but those of Osp primarily by ER alpha. In addition, E-2 and Osp opposed the etoposide-induced increase of IL-6 and decrease of OPG which changes would increase osteoclastic activity. These anti-resorptive effects of E-2 and Osp upon etoposide challenge differed from each other and they seemed to be differentially mediated in ER(x and ER beta expressing osteoblast-derived U2OS cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Kallio, Anu and Guo, Tao and Lamminen, Elisa and Seppanen, Jani and Kangas, Lauri and Vaananen, H. Kalervo and Härkönen, Pirkko},
  issn         = {1872-8057},
  keyword      = {IL-6,OPG,estrogen receptor,estradiol,osteoblast,U2OS},
  language     = {eng},
  number       = {1-2},
  pages        = {38--48},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Estrogen and the selective estrogen receptor modulator (SERM) protection against cell death in estrogen receptor alpha and beta expressing U2OS cells},
  url          = {http://dx.doi.org/10.1016/j.mce.2008.03.005},
  volume       = {289},
  year         = {2008},
}