Estrogen and Cancer

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China and Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, China.
Annual Review of Physiology (Impact Factor: 18.51). 10/2012; 75(1). DOI: 10.1146/annurev-physiol-030212-183708
Source: PubMed


Estrogen exhibits a broad spectrum of physiological functions ranging from regulation of the menstrual cycle and reproduction to modulation of bone density, brain function, and cholesterol mobilization. Despite the beneficial actions of endogenous estrogen, sustained exposure to exogenous estrogen is a well-established risk factor for various cancers. We summarize our current understanding of the molecular mechanisms of estrogen signaling in normal and cancer cells and discuss the major challenges to the existing antiestrogen therapy. Expected final online publication date for the Annual Review of Physiology Volume 75 is February 10, 2013. Please see for revised estimates.

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    • "The binding of estrogen to ERs induces conformational changes in protein structure that allow receptor dimerization and interaction with coactivators. The pro-oncogenic effect of estrogen is mediated primarily by ERα activation of target genes that promote cell proliferation or decrease apoptosis [6]. "
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    ABSTRACT: MicroRNAs play key roles in tumor proliferation and invasion. Here we show distinct expression of miR-222-3p between ERα-positive and ERα-negative endometrial carcinoma (EC) cell lines and primary tumors, and investigation of its relationship with ERα and other clinical parameters. In vitro, the function of miR-222-3p was examined in RL95-2 and AN3CA cell lines. MiR-222-3p expression was negatively correlated with ERα. Over-expressed miR-222-3p in RL95-2 cells promoted cell proliferation, enhanced invasiveness and induced a G1 to S phase shift in cell cycle. Furthermore, the miR-222-3p inhibitor decreased the activity of AN3CA cells to proliferate and invade. In vivo, down-regulated miR-222-3p of AN3CA cells inhibited EC tumor growth in a mouse xenograft model. Additionally, miR-222-3p increased raloxifene resistance through suppressing ERα expression in EC cells. In conclusion, miR-222-3p plays a significant role in the regulation of ERα expression and could be potential targets for restoring ERα expression and responding to antiestrogen therapy in a subset of ECs.
    PLoS ONE 01/2014; 9(1):e87563. DOI:10.1371/journal.pone.0087563 · 3.23 Impact Factor
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    • "Estrogens regulate critical signaling pathways involved in the control of cell proliferation and differentiation in reproductive and non-reproductive tissues (Liang and Shang, 2013). These steroids influence also the pathological processes of hormone-dependent tumors, like breast cancer, activating the estrogen receptor (ER)␣ and ER␤ which act as transcription factors binding to cognate the responsive elements located in the promoter regions of target genes (Ascenzi et al., 2006; Panno et al., 1996). "
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    ABSTRACT: The G protein-coupled receptor GPR30/GPER has been shown to mediate rapid effects of 17β-estradiol (E2) in diverse types of cancer cells. Here, we provide evidence for a novel crosstalk between GPER and the Notch signaling pathway in breast cancer cells and cancer-associated fibroblasts (CAFs). We show that E2 and the GPER selective ligand G-1 induce both the γ-secretase-dependent activation of Notch-1 and the expression of the Notch target gene Hes-1. These inductions are prevented by knocking down GPER or by using a dominant-negative mutant of the Notch transcriptional co-activator Master-mind like-1 (DN-MAML-1), hence suggesting the involvement of GPER in the Notch-dependent transcription. By performing chromatin-immunoprecipitation experiments and luciferase assays, we also demonstrate that E2 and G-1 induce the recruitment of the intracellular domain of Notch-1 (N1ICD) to the Hes-1 promoter and the transactivation of a Hes-1-reporter gene, respectively. Functionally, the E2 and G-1-induced migration of breast cancer cells and CAFs is abolished in presence of the γ-secretase inhibitor GSI or DN-MAML-1, which both inhibit the Notch signaling pathway. In addition, we demonstrate that E2 and G-1 prevent the expression of VE-Cadherin, while both compounds induce the expression of Snail, a Notch target gene acting as a repressor of cadherins expression. Notably, both GSI and DN-MAML-1 abolish the up-regulation of Snail-1 by E2 and G-1, whereas the use of GSI rescues VE-Cadherin expression. Taken together, our results prove the involvement of the Notch signaling pathway in mediating the effects of estrogenic GPER signaling in breast cancer cells and CAFs.
    The international journal of biochemistry & cell biology 11/2013; DOI:10.1016/j.biocel.2013.11.011 · 4.05 Impact Factor
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    ABSTRACT: A growing body of evidence suggests that a subset of orphan nuclear receptors are amplified and prognostic for some human cancers. However, the specific roles of these orphan nuclear receptors in tumor progression and their utility as drug targets are not fully understood. In this review, we summarize recent progress in elucidating the direct and indirect involvement of orphan nuclear receptors in cancer as well as their therapeutic potential in a variety of human cancers. Furthermore, we contrast the role of orphan nuclear receptors in cancer with the known roles of estrogen receptor and androgen receptor in hormone-dependent cancers. Expected final online publication date for the Annual Review of Physiology Volume 76 is February 10, 2014. Please see for revised estimates.
    Annual Review of Physiology 11/2013; 76(1). DOI:10.1146/annurev-physiol-030212-183758 · 18.51 Impact Factor
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