Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer

Lau, Kin‐Mang; To, Ka‐Fai

doi:10.3390/ijms17091434

Cited by 35 publications

(29 citation statements)

References 230 publications

(319 reference statements)

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“…Estrogens, such as diethylstilbestrol (DES), have been proven effective in the hormonal treatment of metastatic prostate cancer more than 70 years ago and are still used as second‐line hormonal therapy. Paradoxically, increasing evidence suggests that estrogens are involved in the development and progression of prostate cancer . The therapeutic efficiency of estrogens results from their systemic endocrine effects acting via the pituitary gland to indirectly decrease testicular androgen secretion at castrate levels.…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression

Bonkhoff¹

2017

The Prostate

140

109

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Background The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. Methods Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. Results The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up‐regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2‐ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. The progressive emergence of the ERα and ERα‐regulated genes (eg, progesterone receptor (PR), PS2, TMPRSS2‐ERG fusion, and NEAT1) during prostate cancer progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. In addition, nongenomic estrogen signaling pathways mediated by orphan receptors (eg, GPR30 and ERRα) has also been implicated in prostate cancer progression. Conclusions Increasing evidences demonstrate that local estrogen signaling mechanisms are required for prostate carcinogenesis and tumor progression. Despite the recent progress in this research topic, the translation of the current information into potential therapeutic applications remains highly challenging and clearly warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression

Bonkhoff¹

2017

The Prostate

140

109

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“…ERβ appears only in human prostate epithelium, while ERα is found predominantly in the stromal compartment (Lau & To 2016). In prostatectomy specimens, higher ERα levels in tumor stroma predicted better PCa survival, while higher ERβ levels in stroma predicted sooner biochemical recurrence.…”

Section: Estrogen and Progesteronementioning

confidence: 97%

Sex steroids in the tumor microenvironment and prostate cancer progression

Boibessot¹,

Toren²

2018

Endocrine-Related Cancer

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Prostate cancer is uniquely dependent on androgens. Despite years of research on the relationship between androgens and prostate cancer, many questions remain as to the biological effects of androgens and other sex steroids during prostate cancer progression. This article reviews the clinical and basic research on the influence of sex steroids such as androgens, estrogens and progesterone within the prostate tumor microenvironment on the progression of prostate cancer. We review clinical studies to date evaluating serum sex steroids as prognostic biomarkers and discuss their respective biological effects within the prostate tumor microenvironment. We also review the link between genomic alterations and sex steroid levels within prostate tumors. Finally, we highlight the links between sex steroid levels and the function of the immune system within the tumor microenvironment. As the context of treatment of lethal prostate cancer evolves over time, an understanding of this underlying biology remains central to developing optimal treatment approaches.

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“…It has been described that estrogens play an important role in in vitro and in vivo models of cancer proliferation. Indeed, several types of tumors synthesize estrogens and express estrogen receptors having a fundamental role in the growth of breast, endometrium, lung and prostate cancer [5,14,15]. Therefore, medication inhibiting estrogen synthesis or regulating estrogen receptor expression is an alternative for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Anastrozole Reduce Cell Proliferation and Induce Apoptosis in Glioblastoma Multiforme Xenograft Mouse Model

García¹,

Ramirez²,

Jiménez³

et al. 2017

J Cancer Sci Ther

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Objective: Glioblastoma multiforme is the most aggressive form of primary brain tumors, characterized by a high molecular heterogeneity hinder its treatment. Glioblastoma multiforme cells synthesize steroids through the enzyme aromatase and express estrogen receptors. Anastrozole, a specific aromatase inhibitor, plays an important role in endocrine therapy for breast cancer treatment. However, it is unknown whether this inhibitor is useful for treating glioblastoma multiforme. The aim of this work was evaluated the anastrozole effects in the viability and proliferation of malignant cells C6 in vitro as well as apoptosis, cell division, aromatase and estrogen receptor alpha expression in a GBM model in vivo.Methods: C6 cells viability under anastrozole treatment (25, 50, 75 µg/ml) was measured by MTT method and their proliferation was determinate by immunohitofluorescence. In the tumor tissue, the proliferation was evaluated using ki-67 antibody by immunohistofluorescence. ER alpha, aromatase, caspase 8 and 9 protein expression was analyzed using western-blotting. Furthermore, GPR-30, SOX2, CD133 and GFAP were evaluated by immunohistofluorescence.Results: Anastrozole produced a reduction in the viability and proliferation of the C6 cells in culture when was used at 50 μg/ml. It reduces the number of Ki67 immunofluorescent cells in approximately 50%. The aromatase expression decreased in 95%. The estrogen receptor alpha expression increased by a 20% approximately. Caspase 8 expression increased in the treated tumor tissue, although it was undetectable in the not treated group. Caspase 9 increased in approximately 95% in the treated group. All data expressed in these experimental quantifications have a statistically significant difference (p<0.05). G protein coupled receptor-30 was observed in the tumor specimens exhibiting an expression reduction in the anastrozole treated group. Conclusion:The present study demonstrates that anastrozole reduces viability and proliferation in vitro, induces apoptosis and reduces proliferation and aromatase expression in the glioblastoma Xenograft mouse model.

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Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer

Cited by 35 publications

References 230 publications

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression

Sex steroids in the tumor microenvironment and prostate cancer progression

Anastrozole Reduce Cell Proliferation and Induce Apoptosis in Glioblastoma Multiforme Xenograft Mouse Model

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