Loss of GPER identifies new targets for therapy among a subgroup of ERα-positive endometrial cancer patients with poor outcome.
Loss of GPER identifies new targets for therapy among a subgroup of ERα-positive endometrial cancer patients with poor outcome.
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DOI：
10.1038/bjc.2012.91
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发表时间：
2012-05-08
影响因子：
8.8
通讯作者：
Salvesen, H. B.
中科院分区：
文献类型：
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作者：
Krakstad, C.;Trovik, J.;Wik, E.;Engelsen, I. B.;Werner, H. M. J.;Birkeland, E.;Raeder, M. B.;Oyan, A. M.;Stefansson, I. M.;Kalland, K. H.;Akslen, L. A.;Salvesen, H. B.
The G protein-coupled oestrogen receptor, GPER, has been suggested as an alternative oestrogen receptor. Our purpose was to investigate the potential of GPER as a prognostic and predictive marker in endometrial carcinoma and to search for new drug candidates to improve treatment of aggressive disease. A total of 767 primary endometrial carcinomas derived from three patient series, including an external dataset, were studied for protein and mRNA expression levels to investigate and validate if GPER loss identifies poor prognosis and new targets for therapy in endometrial carcinoma. Gene expression levels, according to ERα/GPER status, were used to search the connectivity map database for small molecular inhibitors with potential for treatment of metastatic disease for receptor status subgroups. Loss of GPER protein is significantly correlated with low GPER mRNA, high FIGO stage, non-endometrioid histology, high grade, aneuploidy and ERα loss (all P-values ⩽0.05). Loss of GPER among ERα-positive patients identifies a subgroup with poor prognosis that until now has been unrecognised, with reduced 5-year survival from 93% to 76% (P=0.003). Additional loss of GPER from primary to metastatic lesion counterparts further supports that loss of GPER is associated with disease progression. These results support that GPER status adds clinically relevant information to ERα status in endometrial carcinoma and suggest a potential for new inhibitors in the treatment of metastatic endometrial cancers with ERα expression and GPER loss.
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影响因子：
11.2
作者：
Ariazi EA;Brailoiu E;Yerrum S;Shupp HA;Slifker MJ;Cunliffe HE;Black MA;Donato AL;Arterburn JB;Oprea TI;Prossnitz ER;Dun NJ;Jordan VC
通讯作者：
Jordan VC
G蛋白偶联的雌激素受体GPER在健康和疾病中。
DOI：
10.1038/nrendo.2011.122
发表时间：
2011-08-16
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Filardo, EJ;Quinn, JA;Bland, KI
通讯作者：
Bland, KI
影响因子：
45.3
作者：
Salvesen, HB;Iversen, OE;Akslen, LA
通讯作者：
Akslen, LA
影响因子：
4.8
作者：
Gao, Fei;Ma, Xinghong;Das, Sanjoy K.
通讯作者：
Das, Sanjoy K.