Estrogen and the selective estrogen receptor modulator (SERM) protection against cell death in estrogen receptor alpha and beta expressing U2OS cells
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1253847
- author
- Kallio, Anu ; Guo, Tao ; Lamminen, Elisa ; Seppanen, Jani ; Kangas, Lauri ; Vaananen, H. Kalervo and Härkönen, Pirkko LU
- organization
- publishing date
- 2008
- 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
- additional info
- Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:26.
- id
- 1425cda5-5f45-47aa-acb1-2a8825b60e29 (old id 1253847)
- date added to LUP
- 2016-04-01 11:48:00
- date last changed
- 2022-01-26 18:24:36
@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}},
keywords = {{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}},
doi = {{10.1016/j.mce.2008.03.005}},
volume = {{289}},
year = {{2008}},
}