Estrogen promotes increased breast cancer cell proliferation and migration through downregulation of CPEB1 expression

Sovijit, Watcharee; Watcharin, Sovijit; Ishii, Yuriko; Kambe, Jun; Fujita, Tomoyuki; Watanabe, Gen; Yamaguchi, Hirohito; Nagaoka, Kentaro

doi:10.1016/j.bbrc.2020.10.085

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…Consistent with the established pro-mitogenic actions of estrogen, the treatment of MCF-7 cells with estradiol induced cell proliferation [36,37] (Supplementary Data S1). Moreover, the treatment of VECs with estradiol for 3 days increased proliferation by 22 ± 12 (p < 0.05 vs. untreated control), as assessed by the change in cell number (Figure 1a).…”

Section: Effect Of Estrogen and CM On Vec Proliferationsupporting

confidence: 68%

Transcriptomic and Functional Evidence for Differential Effects of MCF-7 Breast Cancer Cell-Secretome on Vascular and Lymphatic Endothelial Cell Growth

Azzarito

Visentin

Leeners

et al. 2022

IJMS

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Vascular and lymphatic vessels drive breast cancer (BC) growth and metastasis. We assessed the cell growth (proliferation, migration, and capillary formation), gene-, and protein-expression profiles of Vascular Endothelial Cells (VECs) and Lymphatic Endothelial Cells (LECs) exposed to a conditioned medium (CM) from estrogen receptor-positive BC cells (MCF-7) in the presence or absence of Estradiol. We demonstrated that MCF-7-CM stimulated growth and capillary formation in VECs but inhibited LEC growth. Consistently, MCF-7-CM induced ERK1/2 and Akt phosphorylation in VECs and inhibited them in LECs. Gene expression analysis revealed that the LECs were overall (≈10-fold) more sensitive to MCF-7-CM exposure than VECs. Growth/angiogenesis and cell cycle pathways were upregulated in VECs but downregulated in LECs. An angiogenesis proteome array confirmed the upregulation of 23 pro-angiogenesis proteins in VECs. In LECs, the expression of genes related to ATP synthesis and the ATP content were reduced by MCF-7-CM, whereas MTHFD2, an immune evasion gene, was upregulated. The contrasting effect of MCF-7-CM on the growth of VECs and LECs was reversed by inhibiting the TGF-β signaling pathway. The effect of MCF-7-CM on VEC growth was also reversed by inhibiting the VEGF signaling pathway. In conclusion, BC secretome may facilitate cancer cell survival and tumor growth by simultaneously promoting vascular angiogenesis and inhibiting lymphatic growth. The differential effects of BC secretome on LECs and VECs may be of pathophysiological relevance in BC.

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Section: Effect Of Estrogen and CM On Vec Proliferationsupporting

confidence: 68%

Transcriptomic and Functional Evidence for Differential Effects of MCF-7 Breast Cancer Cell-Secretome on Vascular and Lymphatic Endothelial Cell Growth

Azzarito

Visentin

Leeners

et al. 2022

IJMS

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“…revealed that the low expression of CPEB1 promoted epithelial-to-mesenchymal transition and metastasis in breast cancer ( 29 ). Interestingly, these malignant phenotypes could be accelerated by estrogen in breast cancer ( 30 ). Previous studies also demonstrated that the low level of CPEB1 was linked to increased metastasis and angiogenesis in gastric cancer (GC), while CPEB1 boosted ferroptosis by inhibiting TWIST1 ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer

et al. 2022

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Breast cancer is a malignancy with the highest incidence and mortality in women worldwide. Senescence is a model of arrest in the cell cycle, which plays an important role in tumor progression, while the prognostic value of cellular senescence-related genes (SRGs) in evaluating immune infiltration and clinical outcomes of breast cancer needs further investigation. In the present study, we identified two distinct molecular subtypes according to the expression profiles of 278 SRGs. We further explored the dysregulated pathways between the two subtypes and constructed a microenvironmental landscape of breast cancer. Subsequently, we established a senescence-related scoring signature based on the expression of four SRGs in the training set (GSE21653) and validated its accuracy in two validation sets (GSE20685 and GSE25055). In the training set, patients in the high-risk group had a worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed that risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The prognostic value of this signature was further confirmed in the validation sets. We also observed that a lower risk score was associated with a higher pathological response rate in patients with neoadjuvant chemotherapy. We next performed functional experiments to validate the results above. Our study demonstrated that these cellular senescence patterns effectively grouped patients at low or high risk of disease recurrence and revealed their potential roles in the tumor–immune–stromal microenvironment. These findings enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the prognosis of breast cancer patients.

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“…41,42 MCF-7 cells expressing estrogen receptors, endogenous estrogen-inducible markers such as progesterone receptor, ps2 protein, and the proliferative effects of estradiol and xenoestrogens on these cells were exerted via estrogen receptor-dependent and independent pathways. 42,43 The estrogenic activity of various pyrethroids including flumethrin was also evaluated using transactivation in vitro assays. 16 Wielogorska et al 16 tested 59 endocrine disrupting agents including pyrethroids for agonism and antagonism to human estrogen receptor via a reporter gene assay using a human mammary gland cell line.…”

Section: Discussionmentioning

confidence: 99%

In vitro toxicological assessment of flumethrin’s effects on MCF-7 breast cancer cells

2021

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Pyrethroid pesticides are frequently used for household insect control of insects and in agriculture and livestock. Flumethrin is a pyrethroid that is used against ectoparasites in many animals. The goal of this study was to evaluate the cytotoxic, apoptotic, genotoxic, and estrogenic effects of flumethrin on the mammalian breast cancer cell line (MCF-7). Compared with control groups, a dose-dependent decrease was observed in cell viability at concentrations of 100 µM and higher. The cytotoxic and apoptotic effects detected by LDH assay and AO/EtBr staining increased significantly at a concentration of 1000 µM. The expression of BCL2, which is an anti-apoptotic gene, significantly decreased, whereas BAX, TP53, and P21 expression significantly increased. The results of a comet assay indicated that flumethrin significantly changed tail length, tail % DNA, tail moment, and Olive tail moment in concentrations above 1 and 10 µM. In addition, a 0.1 µM concentration of flumethrin affected ERα receptor mediated cell proliferation and increased transcription of estrogen-responsive pS2 (TFF1) and progesterone receptor (PGR) genes. As a result, flumethrin-induced apoptosis and cytotoxicity at a high concentration, while induced genotoxicity even at lower concentrations. Flumethrin is an endocrine disrupting insecticide with estrogenic effects at very low concentrations.

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Estrogen promotes increased breast cancer cell proliferation and migration through downregulation of CPEB1 expression

Cited by 6 publications

References 27 publications

Transcriptomic and Functional Evidence for Differential Effects of MCF-7 Breast Cancer Cell-Secretome on Vascular and Lymphatic Endothelial Cell Growth

Transcriptomic and Functional Evidence for Differential Effects of MCF-7 Breast Cancer Cell-Secretome on Vascular and Lymphatic Endothelial Cell Growth

Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer

In vitro toxicological assessment of flumethrin’s effects on MCF-7 breast cancer cells

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