Estrogen Actions in Triple-Negative Breast Cancer

Treeck, Oliver; Schüler-Toprak, Susanne; Ortmann, O.

doi:10.3390/cells9112358

Cited by 50 publications

(52 citation statements)

References 83 publications

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“…Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptor expression and negative amplification of the human epidermal growth factor gene. Approximately 15% of all breast cancers are TNBC, and a poor prognosis fails to identify the disease early in its etiology; thus, TNBC is capable of metastasis prior to diagnosis [5,6]. The current therapies are mostly insufficient to eradicate metastatic cells; therefore, identifying novel mechanisms underlying TNBC development and metastasis and elucidating new treatment targets is critical.…”

Section: Introductionmentioning

confidence: 99%

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

Arısan

Rencüzoğulları

Cieza-Borrella

et al. 2021

IJMS

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Breast cancer (BCa) is one of the leading health problems among women. Although significant achievements have led to advanced therapeutic success with targeted therapy options, more efforts are required for different subtypes of tumors and according to genomic, transcriptomic, and proteomic alterations. This study underlines the role of microRNA-21 (miR-21) in metastatic MDA-MB-231 breast cancer cells. Following the knockout of miR-21 from MDA-MB-231 cells, which have the highest miR-21 expression levels compared to MCF-7 and SK-BR-3 BCa cells, a decrease in epithelial-mesenchymal transition (EMT) via downregulation of mesenchymal markers was observed. Wnt-11 was a critical target for miR-21, and the Wnt-11 related signaling axis was altered in the stable miR-21 knockout cells. miR-21 expression was associated with a significant increase in mesenchymal markers in MDA-MB-231 BCa cells. Furthermore, the release of extracellular vesicles (EVs) was significantly reduced in the miR-21 KO cells, alongside a significant reduction in relative miR-21 export in EV cargo, compared with control cells. We conclude that miR-21 is a leading factor involved in mesenchymal transition in MDA-MB-231 BCa. Future therapeutic strategies could focus on its role in the treatment of metastatic breast cancer.

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Section: Introductionmentioning

confidence: 99%

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

Arısan

Rencüzoğulları

Cieza-Borrella

et al. 2021

IJMS

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“…In the case of breast cancer, estrogen primarily acts through ER-α [ 18 ]. The clinical significance of ER-β remains unelucidated [ 13 ], but several data indicate its tumor-suppressive properties [ 20 , 21 ]. The ER signaling pathway promotes unequal rates of division and apoptosis in cancer cells, supporting the pro-survival signals over the pro-death ones [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, its presence indicates a positive response to HER2-targeted treatment [ 26 ]. The triple-negative breast cancer (TNBC) is characterized by an aggressive behavior, with early relapse and metastatic spread to several organs such as lung, liver, and brain [ 27 ], being responsible for more than 50% of the breast cancer-related deaths [ 21 ]. TNBC is uniquely defined by the absence of hormone receptors (ER-α/PRs) and negativity for HER2, accounting for approximately 10–15% of all breast cancer diagnoses [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Insights into the Behavior of Triple-Negative MDA-MB-231 Breast Carcinoma Cells Following the Treatment with 17β-Ethinylestradiol and Levonorgestrel

et al. 2021

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Oral contraceptives (OCs) are widely used due to their efficiency in preventing unplanned pregnancies and treating several human illnesses. Despite their medical value, the toxicity of OCs remains a public concern. Previous studies indicate the carcinogenic potential of synthetic sex hormones and their link to the development and progression of hormone-dependent malignancies such as breast cancer. However, little is known about their influence on the evolution of triple-negative breast carcinoma (TNBC), a malignancy defined by the absence of estrogen, progesterone, and HER2 receptors. This study reveals that the active ingredients of modern OCs, 17β-Ethinylestradiol, Levonorgestrel, and their combination induce differential effects in MDA-MB-231 TNBC cells. The most relevant behavioral changes occurred after the 24 h treatment with 17β-Ethinylestradiol, summarized as follows: (i) decreased cell viability (64.32% at 10 µM); (ii) cell roundness and loss of confluence; (iii) apoptotic aspect of cell nuclei (fragmentation, membrane blebbing); and (iv) inhibited cell migration, suggesting a potential anticancer effect. Conversely, Levonorgestrel was generally associated with a proliferative activity. The association of the two OCs exerted similar effects as 17β-Ethinylestradiol but was less effective. Further studies are necessary to elucidate the hormones’ cytotoxic mechanism of action on TNBC cells.

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“…The significance of GPER1 expression related to ER-positive breast cancer and in TNBC has been investigated. GPER1 has been detected in about 50 to 60% of breast cancer tissues [ 35 ]. Among these, GPER1 expression has been evidenced in the majority of TNBC, whereas co-expression of GPER1 and ER was about 40% of all cases examined [ 35 ].…”

Section: Gper1 History Expression and Localizationmentioning

confidence: 99%

“…GPER1 has been detected in about 50 to 60% of breast cancer tissues [ 35 ]. Among these, GPER1 expression has been evidenced in the majority of TNBC, whereas co-expression of GPER1 and ER was about 40% of all cases examined [ 35 ]. Notably, in patients treated with tamoxifen the expression of GPER1 was found increased and associated with a poor prognosis and relapse-free survival, suggesting that GPER1 expression in ER-positive breast cancer is correlated to tamoxifen resistance [ 36 ].…”

Section: Gper1 History Expression and Localizationmentioning

confidence: 99%

GPER1 and microRNA: Two Players in Breast Cancer Progression

Vivacqua

2020

IJMS

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Breast cancer is the main cause of morbidity and mortality in women worldwide. However, the molecular pathogenesis of breast cancer remains poorly defined due to its heterogeneity. Several studies have reported that G Protein-Coupled Estrogen Receptor 1 (GPER1) plays a crucial role in breast cancer progression, by binding to estrogens or synthetic agonists, like G-1, thus modulating genes involved in diverse biological events, such as cell proliferation, migration, apoptosis, and metastasis. In addition, it has been established that the dysregulation of short sequences of non-coding RNA, named microRNAs (miRNAs), is involved in various pathophysiological conditions, including breast cancer. Recent evidence has indicated that estrogens may regulate miRNA expression and therefore modulate the levels of their target genes, not only through the classical estrogen receptors (ERs), but also activating GPER1 signalling, hence suggesting an alternative molecular pathway involved in breast tumor progression. Here, the current knowledge about GPER1 and miRNA action in breast cancer is recapitulated, reporting recent evidence on the liaison of these two players in triggering breast tumorogenic effects. Elucidating the role of GPER1 and miRNAs in breast cancer might provide new tools for innovative approaches in anti-cancer therapy.

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Estrogen Actions in Triple-Negative Breast Cancer

Cited by 50 publications

References 83 publications

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

MiR-21 Is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells

Insights into the Behavior of Triple-Negative MDA-MB-231 Breast Carcinoma Cells Following the Treatment with 17β-Ethinylestradiol and Levonorgestrel

GPER1 and microRNA: Two Players in Breast Cancer Progression

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