Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

Elo, Teresa; Yu, Lan; Valve, Eeva; Mäkelä, Sari; Härkönen, Pirkko

doi:10.1530/erc-13-0480

Cited by 3 publications

(4 citation statements)

References 63 publications

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“…Specifically, it was reported recently that deletion of ERβ in the FGF8b transgenic model of prostate tumorigenesis did not increase tumor incidence (Elo et al, 2014). Although the authors discounted a tumor suppressive role for ERβ based on these data, this conclusion should be tempered by the likely possibility that FGF8b-mediated tumorigenesis involves repression of ERβ, similar to our finding with prostate tumorigenesis caused by PTEN deletion.…”

Section: Discussionmentioning

confidence: 99%

“…These mice do not develop prostate cancer (Antal et al, 2008; Imamov et al, 2004), although some studies have observed prostate hyperplasia in older BERKO mice (Imamov et al, 2004). Furthermore, deletion of ERβ in the FGF8b transgenic model of prostate tumorigenesis did not increase tumor incidence, a finding that has been used to discount a tumor suppressive function for ERβ (Elo et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Prostate Tumorigenesis Induced by PTEN Deletion Involves Estrogen Receptor β Repression

et al. 2015

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The role of ERβ in prostate cancer is unclear, although its loss of ERβ is associated with aggressive disease. Given that mice deficient in ERβ do not develop prostate cancer, we hypothesized that ERβ loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERβ is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERβ is important for tumor formation. ERβ transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. This finding provides a mechanism for how ERβ expression is regulated in prostate cancer. Repression of ERβ contributes to tumorigenesis because it enables HIF-1/VEGF signaling that sustains BMI-1 expression. These data reveal a positive feedback loop that is activated in response to PTEN loss and sustains BMI-1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prostate Tumorigenesis Induced by PTEN Deletion Involves Estrogen Receptor β Repression

et al. 2015

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“…The role of ERβ in oppressing androgen receptor signaling, and suppressing proliferation and inflammation, suggests that ERβ may be a potential therapeutic target to prevent the progression of prostate cancer (30). Differentiation of prostatic epithelial cells, in which ERβ serves a significant role, is a defensive mechanism required for the protection against inflammation in the prostate of FGF8b transgenic mice (31). The findings of the present study revealed that ERβ overexpression reduced the upregulated expression levels of TNF-α, MCP-1, IL-6 and IL-1β in PC-3 cells induced by LPS, indicating a potential therapeutic role of ERβ in the reduction of inflammation in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β suppresses inflammation and the progression of prostate cancer

et al. 2019

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Previous studies demonstrated that estrogen receptor β (ERβ) signaling alleviates systemic inflammation in animal models, and suggested that ERβ-selective agonists may deactivate microglia and suppress T cell activity via downregulation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). In the present study, the role of ERβ in lipopolysaccharide (LPS)-induced inflammation and association with NF-κB activity were investigated in PC-3 and DU145 prostate cancer cell lines. Cells were treated with LPS to induce inflammation, and ELISA was performed to determine the expression levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-1β and IL-6. MTT and Transwell assays, and Annexin V/propidium iodide staining were conducted to measure cell viability, apoptosis and migration, respectively. Protein expression was determined via western blot analysis. LPS-induced inflammation resulted in elevated expression levels of TNF-α, IL-1β, MCP-1 and IL-6 compared with controls. ERβ overexpression significantly inhibited the LPS-induced production of TNF-α, IL-1β, MCP-1 and IL-6. In addition, the results indicated that ERβ suppressed viability and migration, and induced apoptosis in prostate cancer cells, which was further demonstrated by altered expression of proliferating cell nuclear antigen, B-cell lymphoma 2-associated X protein, caspase-3, E-cadherin and matrix metalloproteinase-2. These effects were reversed by treatment with the ERβ antagonist PHTPP or ERβ-specific short interfering RNA. ERβ overexpression reduced the expression levels of p65 and phosphorylated NF-κB inhibitor α (IκBα), but not total IκBα expression in LPS-treated cells. In conclusion, ERβ suppressed the viability and migration of the PC-3 and DU145 prostate cancer cell lines and induced apoptosis. Furthermore, it reduced inflammation and suppressed the activation of the NF-κB pathway, suggesting that ERβ may serve roles as an anti-inflammatory and anticancer agent in prostate cancer.

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“…One study described CAF ERa and ERb expression as a marker of clinically advanced disease. 50 On the other hand, some studies have shown that estrogen-sensitive CAFs can suppress tumor growth, invasion, and metastasis through reduced IL-6 and C-C motif chemokine ligand 5 expression. 51,52 Innate Immune Cells…”

Section: Stromamentioning

confidence: 99%

Estrogen Regulation of T-Cell Function and Its Impact on the Tumor Microenvironment

Navarro

Herrnreiter

Nowak

et al. 2018

Gender and the Genome

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Epidemiologic studies demonstrate significant gender-specific differences in immune system function. Males are more prone to infection and malignancies, while females are more vulnerable to autoimmune diseases. These differences are thought to be due to the action of gonadal hormones: Estrogen increases the inflammatory response and testosterone dampens it. More specifically, estrogen stimulation induces inflammatory cytokine production including interferon g, interleukin (IL) 6, and tumor necrosis factor a, while testosterone induces IL-10, IL-4, and transforming growth factor b. More recent studies demonstrate threshold effects of estrogen stimulation on immune cell function: physiologic doses of estrogen (approximately 0.5 nmol/L) stimulate inflammatory cytokine production, but superphysiologic dosages (above 50 nmol/L) can result in decreased inflammatory cytokine production. This review reports findings concerning the impact of estrogen on CD8 þ cytotoxic T cells and the overall immune response in the tumor microenvironment. Variables examined include dosage of hormone, the diversity of immune cells involved, and the nature of the immune response in cancer. Collective review of these points may assist in future hypotheses and studies to determine sex-specific differences in immune responses that may be used as targets in disease prevention and treatment.

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Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

Cited by 3 publications

References 63 publications

Prostate Tumorigenesis Induced by PTEN Deletion Involves Estrogen Receptor β Repression

Prostate Tumorigenesis Induced by PTEN Deletion Involves Estrogen Receptor β Repression

Estrogen receptor β suppresses inflammation and the progression of prostate cancer

Estrogen Regulation of T-Cell Function and Its Impact on the Tumor Microenvironment

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