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The G protein-coupled estrogen receptor 1 (GPER/GPR30) does not predict survival in patients with ovarian cancer

Kolkova, Zuzana LU ; Casslén, Vera LU ; Henic, Emir LU ; Ahmadi, Sara LU ; Ehinger, Anna LU ; Jirström, Karin LU and Casslén, Bertil LU (2012) In Journal of Ovarian Research 5.
Abstract
Background: Even though ovarian tumors are not generally considered estrogen-sensitive, estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane estrogen receptor GPER is involved in rapid estrogen signaling. Furthermore, it binds selective estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies. Methods: GPER mRNA was assayed with quantitative real-time PCR (qPCR) in 42 primary ovarian tumors and 7 ovarian cancer cell lines. ER alpha and ER beta mRNA were analyzed for comparison. GPER protein was semi-quantified with densitometric scanning of Western blots and its tissue distribution analyzed with immunohistochemistry (IHC) in 40 ovarian tumors. In... (More)
Background: Even though ovarian tumors are not generally considered estrogen-sensitive, estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane estrogen receptor GPER is involved in rapid estrogen signaling. Furthermore, it binds selective estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies. Methods: GPER mRNA was assayed with quantitative real-time PCR (qPCR) in 42 primary ovarian tumors and 7 ovarian cancer cell lines. ER alpha and ER beta mRNA were analyzed for comparison. GPER protein was semi-quantified with densitometric scanning of Western blots and its tissue distribution analyzed with immunohistochemistry (IHC) in 40 ovarian tumors. In addition, IHC was evaluated in a tissue microarray (TMA) of 150 primary malignant ovarian tumors. Results: All tumor samples contained GPER mRNA. The content of mRNA was not different between benign and malignant tumors, but one third of malignant samples over-expressed GPER mRNA. The content of ER alpha mRNA was higher in malignant than in benign tumors, whereas ER beta mRNA was higher in benign than in malignant tumors. GPER mRNA was detected in all seven ovarian cancer cell lines with highest levels in TOV21G and TOV112D cells. Similar expression pattern was seen for ER beta mRNA. Western blot demonstrated GPER protein in all tumor samples. Semi-quantification showed no difference between benign and malignant tumors, but about one third of malignant samples over-expressed GPER protein. GPER staining was localized mainly in epithelial cells. In the TMA study we found no correlation between GPER staining and clinical stage, histological grade or patient survival. Conclusions: GPER mRNA as well as GPER protein is present in both benign and malignant ovarian tumor tissue. About one third of malignant tumors over-expressed both GPER mRNA and protein. This, however, correlated neither with histological or clinical parameters nor with patient survival. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ER alpha, ER beta, borderline tumors, TMA, immunohistochemistry, ovarian, cancer cell lines
in
Journal of Ovarian Research
volume
5
publisher
BioMed Central
external identifiers
  • wos:000304043700001
  • scopus:84858201263
ISSN
1757-2215
DOI
10.1186/1757-2215-5-9
language
English
LU publication?
yes
id
ba02dde6-13b0-4a76-b757-69ae3fbefc58 (old id 2826821)
date added to LUP
2012-07-03 10:26:02
date last changed
2017-09-24 04:12:08
@article{ba02dde6-13b0-4a76-b757-69ae3fbefc58,
  abstract     = {Background: Even though ovarian tumors are not generally considered estrogen-sensitive, estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane estrogen receptor GPER is involved in rapid estrogen signaling. Furthermore, it binds selective estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies. Methods: GPER mRNA was assayed with quantitative real-time PCR (qPCR) in 42 primary ovarian tumors and 7 ovarian cancer cell lines. ER alpha and ER beta mRNA were analyzed for comparison. GPER protein was semi-quantified with densitometric scanning of Western blots and its tissue distribution analyzed with immunohistochemistry (IHC) in 40 ovarian tumors. In addition, IHC was evaluated in a tissue microarray (TMA) of 150 primary malignant ovarian tumors. Results: All tumor samples contained GPER mRNA. The content of mRNA was not different between benign and malignant tumors, but one third of malignant samples over-expressed GPER mRNA. The content of ER alpha mRNA was higher in malignant than in benign tumors, whereas ER beta mRNA was higher in benign than in malignant tumors. GPER mRNA was detected in all seven ovarian cancer cell lines with highest levels in TOV21G and TOV112D cells. Similar expression pattern was seen for ER beta mRNA. Western blot demonstrated GPER protein in all tumor samples. Semi-quantification showed no difference between benign and malignant tumors, but about one third of malignant samples over-expressed GPER protein. GPER staining was localized mainly in epithelial cells. In the TMA study we found no correlation between GPER staining and clinical stage, histological grade or patient survival. Conclusions: GPER mRNA as well as GPER protein is present in both benign and malignant ovarian tumor tissue. About one third of malignant tumors over-expressed both GPER mRNA and protein. This, however, correlated neither with histological or clinical parameters nor with patient survival.},
  author       = {Kolkova, Zuzana and Casslén, Vera and Henic, Emir and Ahmadi, Sara and Ehinger, Anna and Jirström, Karin and Casslén, Bertil},
  issn         = {1757-2215},
  keyword      = {ER alpha,ER beta,borderline tumors,TMA,immunohistochemistry,ovarian,cancer cell lines},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Journal of Ovarian Research},
  title        = {The G protein-coupled estrogen receptor 1 (GPER/GPR30) does not predict survival in patients with ovarian cancer},
  url          = {http://dx.doi.org/10.1186/1757-2215-5-9},
  volume       = {5},
  year         = {2012},
}