G protein-coupled receptor 30 in tumor development

Wang, Dengfeng; Hu, Lina; Zhang, Guonan; Zhang, Lin; Chen, Chen

doi:10.1007/s12020-010-9363-z

Cited by 74 publications

(55 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GPR30 signaling contributes to tumor growth and resistance to antiestrogen in breast cancers (51). Furthermore, GPR30 cooperates with EGFR/HER2, a gene known to be overexpressed in endocrine-resistant breast cancer, to mediate signaling pathway activation and cell proliferation (52,53).…”

Section: Discussionmentioning

confidence: 99%

LRH-1 Governs Vital Transcriptional Programs in Endocrine-Sensitive and -Resistant Breast Cancer Cells

Bianco

Brunelle²,

Jangal

et al. 2014

Cancer Research

View full text Add to dashboard Cite

Tumor characteristics are decisive in the determination of treatment strategy for patients with breast cancer. Patients with estrogen receptor a (ERa)-positive breast cancer can benefit from long-term hormonal treatment. Nonetheless, the majority of patients will develop resistance to these therapies. Here, we investigated the role of the nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in antiestrogen-sensitive and -resistant breast cancer cells. We identified genome-wide LRH-1-binding sites using ChIP-seq (chromatin immunoprecipitation sequencing), uncovering preferential binding to regions distal to transcriptional start sites. We further characterized these LRH-1-binding sites by integrating overlapping layers of specific chromatin marks, revealing that many LRH-1-binding sites are active and could be involved in long-range enhancer-promoter looping. Combined with transcriptome analysis of LRH-1-depleted cells, these results show that LRH-1 regulates specific subsets of genes involved in cell proliferation in antiestrogen-sensitive and antiestrogen-resistant breast cancer cells. Furthermore, the LRH-1 transcriptional program is highly associated with a signature of poor outcome and high-grade breast cancer tumors in vivo. Herein, we report the genome-wide location and molecular function of LRH-1 in breast cancer cells and reveal its therapeutic potential for the treatment of breast cancers, notably for tumors resistant to treatments currently used in therapies. Cancer Res; 74(7); 2015-25. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

LRH-1 Governs Vital Transcriptional Programs in Endocrine-Sensitive and -Resistant Breast Cancer Cells

Bianco

Brunelle²,

Jangal

et al. 2014

Cancer Research

View full text Add to dashboard Cite

show abstract

“…In addition, GPR30 is involved in drug resistance, which is often occurring during cancer treatment. Hence, simultaneous blocking both GPR30 and classic ERs may be a better strategy for the treatment of schistosomiasis-related cancer and infertility [46].…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes

Botelho

Alves

Barros

et al. 2015

Trends in Parasitology

View full text Add to dashboard Cite

“…GPR30 is independent of ERα status in breast cancer cells and tissue samples, and its action differs from the classical nuclear ERs, ERα and ERβ (32). Upregulation and activation of GPR30 promotes the progression of breast cancer, and GPR30 is considered a biological target for innovative therapeutic strategies (33). Research has demonstrated that overexpression of GPR30 in primary tumors is positively correlated with the metastatic phenotype of breast cancer (6,7), and GPR30 knockout MMTV-PyMT mice possess less aggressive tumors and fewer metastases (8).…”

Section: Discussionmentioning

confidence: 99%

Baicalein, unlike 4-hydroxytamoxifen but similar to G15, suppresses 17β-estradiol-induced cell invasion, and matrix metalloproteinase-9 expression and activation in MCF-7 human breast cancer cells

et al. 2017

View full text Add to dashboard Cite

Abstract.Estrogen performs an important role in the growth and development of breast cancer. There are at least three major receptors, including estrogen receptor (ER)α and β, and G protein-coupled receptor 30 (GPR30), which mediate the actions of estrogen through using transcriptional and rapid non-genomic signaling pathways. Flavonoids have been considered candidates for chemopreventive agents in breast cancer. Baicalein, the primary flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported to exert an anti-estrogenic effect. In the present study, the effects of baicalein on 17β-estradiol (E2)-induced cell invasion, and matrix metalloproteinase-9 (MMP-9) expression and activation were investigated. Furthermore, its effects were compared with that of the active form of the ER modulator tamoxifen 4-hydroxytamoxifen (OHT) and the GPR30 antagonist G15 in ERα-and GPR30-positive MCF-7 breast cancer cells. The results demonstrated that OHT failed to prevent E2-induced cell invasion, upregulation and proteolytic activity of MMP-9. However, baicalein was able to significantly suppress these E2-induced effects. Furthermore, E2-stimulated invasion, and MMP-9 expression and activation were significantly attenuated following G15 treatment. In addition, baicalein significantly inhibited G-1, a specific GPR30 agonist, induced invasion, and reduced G-1 promoted expression and activity of MMP-9, consistent with effects of G15. The results of the present study suggest that baicalein is a therapeutic candidate for GPR30-positive breast cancer treatment, and besides ERα targeting the GPR30 receptor it may achieve additional therapeutic benefits in breast cancer. IntroductionIt is well known that the steroid hormone estrogen performs a role in the pathogenesis of breast cancer, and the majority of breast cancer types involve estrogen signaling pathways in cancer initiation, progression and metastasis (1). The majority of estrogen-associated biological actions are traditionally attributed to activate classic estrogen receptors (ERs), ERα and ERβ (2). Thus, endocrine therapies that interfere with ER functions are currently applied in patients with ER-positive breast cancer. Although targeted inhibition of ERα is a successful approach, numerous patients fail to respond (de novo resistance) or relapse despite an initial response (acquired resistance) to anti-estrogen therapy (3). The selective ER modulator tamoxifen, which antagonizes estrogen-induced genomic-nuclear ERα activity, is widely used in the treatment of ERα-positive breast cancer. It has significantly reduced the mortality risk among patients, however, not all patients achieve beneficial effects as disease recurrence occurs in ~25-30% of patients (4).The identification and characterization of the G protein-coupled receptor 30 (GPR30) represents an additional mechanism of estrogen effects, which mediate a wide range of estrogenic responses, leading to changes in gene expression and relevant biological responses (5). It has been revealed that GPR30...

show abstract

G protein-coupled receptor 30 in tumor development

Cited by 74 publications

References 80 publications

LRH-1 Governs Vital Transcriptional Programs in Endocrine-Sensitive and -Resistant Breast Cancer Cells

LRH-1 Governs Vital Transcriptional Programs in Endocrine-Sensitive and -Resistant Breast Cancer Cells

The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes

Baicalein, unlike 4-hydroxytamoxifen but similar to G15, suppresses 17β-estradiol-induced cell invasion, and matrix metalloproteinase-9 expression and activation in MCF-7 human breast cancer cells

Contact Info

Product

Resources

About