Role of GPR30 in the mechanisms of tamoxifen resistance in breast cancer MCF-7 cells

Ignatov, Atanas; Ignatov, Tanja; Roessner, Albert; Costa, Serban Dan; Kalinski, Thomas

doi:10.1007/s10549-009-0624-6

Cited by 141 publications

(138 citation statements)

References 33 publications

(49 reference statements)

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…However, the authors stated that EGFR expression in combination with GPER-1 predicts lower survival in patients with ovarian cancer. This is in agreement with our recent results demonstrating that GPER-1 cross-talks with EGFR in breast cancer cell lines [22]. The cross-talk between GPER-1 and EGFR is associated with activation of completely different signalling pathways [5,6,23] and could be responsible for the observed difference in survival rates.…”

Section: Discussionsupporting

confidence: 93%

GPER-1 acts as a tumor suppressor in ovarian cancer

Seiz¹,

Ignatov²,

Weißenborn³

et al. 2014

Geburtshilfe Frauenheilkd

View full text Add to dashboard Cite

Background: It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells. Patients and methods: GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth. Results: GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3. Conclusion: GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer.

show abstract

Section: Discussionsupporting

confidence: 93%

GPER-1 acts as a tumor suppressor in ovarian cancer

Seiz¹,

Ignatov²,

Weißenborn³

et al. 2014

Geburtshilfe Frauenheilkd

View full text Add to dashboard Cite

show abstract

“…This may be a possible mechanism for tamoxifen resistance in some of the ER-positive breast cancers that express high levels of GPER. Consistently, overexpression of GPER in MCF7 breast cancer cells indeed increases tamoxifen resistance (49). Furthermore, there are clinical data showing that GPER is involved in tamoxifen resistance in breast cancer (12).…”

Section: Methodsmentioning

confidence: 63%

Estrogen regulates Hippo signaling via GPER in breast cancer

et al. 2015

View full text Add to dashboard Cite

“…Some investigators have suggested that GPER1 contributes to tamoxifen resistance based on observations that tamoxifen stimulates GPER1 in vitro (10,11) and that GPER1 is upregulated in tamoxifen-resistant MCF7 cells (46). However, GPER1 has not appeared in functional screens for genes contributing to tamoxifen-resistance in breast cancer cells (47,48).…”

Section: Discussionmentioning

confidence: 99%

G Protein–Coupled Estrogen Receptor Is Apoptotic and Correlates with Increased Distant Disease-Free Survival of Estrogen Receptor–Positive Breast Cancer Patients

Broselid

Cheng

Sjöström

et al. 2013

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: G protein–coupled estrogen receptor 1 (GPER1), previously named GPR30, is a membrane receptor reported to mediate nongenomic estrogen responses. We investigated if GPER1 expression correlates with any clinicopathologic variables and distant disease-free survival (DDFS) in patients with breast cancer, if any prognostic impact of the receptor is dependent on estrogen receptor-α (ER-α) status, and if the receptor impacts apoptotic signaling in ER-positive breast cancer cells. Experimental Design: GPER1 expression was analyzed by immunohistochemistry in breast tumors from 273 pre- and postmenopausal stage II patients, all treated with adjuvant tamoxifen for 2 years (cohort I) and from 208 premenopausal lymph node-negative patients, of which 87% were not subjected to any adjuvant systemic treatment (cohort II). GPER1-dependent proapoptotic signaling was analyzed in MCF7 cells with and without GPER1 knockdown, T47D cells, HEK293 cells (HEK), and HEK stably expressing GPER1 (HEK-R). Results: GPER1 positively correlates with ER and progesterone receptor expression. Multivariate analysis showed that GPER1 is an independent prognostic marker of increased 10-year DDFS in the ER-positive subgroup. HEK-R has higher basal proapoptotic signaling compared with HEK including increased cytochrome C release, caspase-3 cleavage, PARP cleavage, and decreased cell viability. Treating HEK-R with the proteasome inhibitor epoxomicin, to decrease GPER1 degradation, further increases receptor-dependent proapoptotic signaling. Also, GPER1 knockdown decreases basal and agonist-stimulated proapoptotic receptor signaling in MCF7 cells. Conclusions: GPER1 is a prognostic indicator for increased DDFS in ER-positive breast cancer, which may be associated with constitutive GPER1-dependent proapoptotic signaling in ER-positive breast cancer cells. Clin Cancer Res; 19(7); 1681–92. ©2013 AACR.

show abstract

Role of GPR30 in the mechanisms of tamoxifen resistance in breast cancer MCF-7 cells

Cited by 141 publications

References 33 publications

GPER-1 acts as a tumor suppressor in ovarian cancer

GPER-1 acts as a tumor suppressor in ovarian cancer

Estrogen regulates Hippo signaling via GPER in breast cancer

G Protein–Coupled Estrogen Receptor Is Apoptotic and Correlates with Increased Distant Disease-Free Survival of Estrogen Receptor–Positive Breast Cancer Patients

Contact Info

Product

Resources

About