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smad estrogen

Anushka Dikshit, Karen Hales, Dale Buchanan Hales
The study reported here demonstrates that a flaxseed-supplemented diet causes ovarian tumors in the laying hen to undergo apoptosis, resulting in a reduction of tumor burden, reducing the frequency and severity of ovarian cancer. We have previously shown in normal ovaries that flaxseed and its components down-regulate ERalpha and alter the expression of enzymes that metabolize estrogen. In this study, we analyzed the effects of the two main components of whole flaxseed, ligan and omega 3 fatty acids on estrogen metabolism and the estrogen receptor in ovarian tumors...
April 2017: Journal of Nutritional Biochemistry
Juan Zheng, Juan Qu, Pinhong Lu, Zhen Hou, Yugui Cui, Yundong Mao, Xiaochen Qi, Hui Ji, Jiayin Liu
Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was regulated by the Activin-Smad pathway in endometrial lesions. The data showed that the effect of Activin A on ESCs was partially abrogated by pretreatment with an inhibitor of ALK4 (the type I receptor, ActRIB) and Smad4-siRNA...
2016: BioMed Research International
Fabrice G Petit, Chuxia Deng, Soazik P Jamin
Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme...
2016: International Journal of Biological Sciences
Diana Monsivais, Caterina Clementi, Jia Peng, Mary M Titus, James P Barrish, Chad J Creighton, John P Lydon, Francesco J DeMayo, Martin M Matzuk
The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy...
January 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yang Yang, Yaxian Wang, Lixia Du, Huayan Wang
The estrogen related receptor family member Esrrb (Estrogen related receptor β) is a gene that expresses in the early stage of embryo and plays an important role in the core pluripotent network. Its function has been analyzed in human and mouse, although no report so far related to pig. Therefore, to explore its mechanism of transcriptional regulation and expression pattern, we cloned a 3.3 kb pig ESRRB promoter by PCR and constructed the green fluorescence protein (GFP) reporter vector pE3.3. We used these vectors to study the ESRRB expression pattern in 293T, Hela and C2C12...
April 2015: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Lin Deng, Francisco J Blanco, Hannah Stevens, Ruifang Lu, Axelle Caudrillier, Martin McBride, John D McClure, Jenny Grant, Matthew Thomas, Maria Frid, Kurt Stenmark, Kevin White, Anita G Seto, Nicholas W Morrell, Angela C Bradshaw, Margaret R MacLean, Andrew H Baker
RATIONALE: The pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. The 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. OBJECTIVE: To elucidate the transcriptional regulation of the miR-143/145 cluster and the role of miR-143 in PAH. METHODS AND RESULTS: We identified the promoter region that regulates miR-143/145 microRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic X receptor, transforming growth factor-β (Smads), and hypoxia (hypoxia response element), that regulated levels of all pri-miR stem loop transcription and resulting microRNA expression...
October 23, 2015: Circulation Research
K Bacallao, F Plaza-Parrochia, A Cerda, F Gabler, C Romero, D Vantman, M Vega
Polycystic ovarian syndrome (PCOS) has been associated with endometrial hyperplasia and cancer. The aim of this study was to establish whether the expression of proliferation regulatory proteins in the endometria of patients having PCOS, with or without hyperplasia, differs from control women. Control endometria (CE), patients having PCOS without and with endometrial hyperplasia (PCOSE and HPCOSE, respectively), and that of women with endometrial hyperplasia (HE) were used. The phosphorylated estrogen receptor form (pERα), similar to mother against decapentaplegic (SMAD) 2, SMAD3, and SMAD4, vascular epithelial growth factor (VEGF), and phosphorylated SMAD (pSMAD) 2 and pSMAD3 were detected by immunohistochemistry or Western blot...
February 2016: Reproductive Sciences
He-Song Jiang, Lei-Lei Zhu, Zheng Zhang, Hai Chen, Yun Chen, Yu-Tian Dai
The transformation of tunica albuginea-derived fibroblasts (TAFs) into myofibroblasts plays an important role in the pathological progress of Peyronie's disease (PD). However, no treatment which addresses this transformation is currently available. Estrogen has been shown to inhibit the progression of fibrosis in a number of fibrotic diseases. The aim of this study was to determine whether estrogen [17β‑estradiol (E2)] suppresses the diffentiation of primary rat TAFs into myofibroblasts in vitro. TAFs obtained from male Sprague‑Dawley rats were stimulated with either transforming growth factor‑β1 (TGF‑β1) or E2...
September 2015: International Journal of Molecular Medicine
Mostafa A Borahay, Ayman Al-Hendy, Gokhan S Kilic, Darren Boehning
Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial...
2015: Molecular Medicine
Ri Youn Kim, Hoon Joo Yang, Yun Mi Song, In Sook Kim, Soon Jung Hwang
Clinical data show that estrogen levels are inversely associated with the production of sclerostin, a Wnt antagonist that recently attracted great attention over the use of its antibody in the anabolic treatment of osteoporotic conditions. However, the molecular link between sclerostin expression and estrogen signaling is not yet known. We investigated the mechanisms by which estrogen modulates sclerostin (SOST) gene expression at the cellular level in human osteoblast cells in association with bone morphogenetic protein (BMP)2 signaling given that BMP2 is a potential inducer of SOST in human mesenchymal stromal cells (hMSCs)...
July 2015: Tissue Engineering. Part A
Zhenye Li, Qian Liu, Chuzhong Li, Xuyi Zong, Jiwei Bai, Youtu Wu, Xiaolei Lan, Guoqiang Yu, Yazhuo Zhang
BACKGROUND: Prolactinomas are the most common secretory pituitary adenomas. The first line of treatment involves dopamine agonists (DAs); however, a subset of patients is resistant to such therapy. Recent studies suggest that dopamine can up-regulate TGF-β1 synthesis in rat pituitary lactotrophs whereas estradiol down-regulates TGF-β1. To date, the role of TGF-β/Smad signaling in DAs-resistant prolactinomas has not been explored. METHODS: High-content screening (HCS) techniques, qRT-PCR, Western blot, immunofluorescence and ELISA, were performed to determine the role of TGF-β/Smad signaling in DAs-resistant prolactinomas...
February 15, 2015: Molecular and Cellular Endocrinology
Guiting Lin, Amjad Alwaal, Fionna Sun, Haiyang Zhang, Huixi Li, Lin Wang, Guifang Wang, Hongxiu Ning, Lia Banie, Ching-Shwun Lin, Tom F Lue
PURPOSE: We investigated the effect and mechanism of estrogen on elastogenesis in urethral smooth muscle cells in vitro. MATERIALS AND METHODS: Urethral smooth muscle cells were isolated from normal adult female rats. For elastogenesis assay cells were treated with TGF-β1, the potent TGF-β1 receptor inhibitor SB431542 and estrogen for 2 weeks. Real-time polymerase chain reaction was performed to assay gene expression during this process. Activity of the TGF-β1 responsive elements CAGA(12)-Luc and GCCG(12)-Luc were also assayed...
June 2015: Journal of Urology
Jimin Guo, Lucie Canaff, Charles Vincent Rajadurai, Nadège Fils-Aimé, Jun Tian, Meiou Dai, Juliana Korah, Manuel Villatoro, Morag Park, Suhad Ali, Jean-Jacques Lebrun
INTRODUCTION: This study helps to define the implications of breast cancer anti-estrogen resistance 3 (BCAR3) in breast cancer and extends the current understanding of its molecular mechanism of action. BCAR3 has been shown to promote cell proliferation, migration and attachment to extracellular matrix components. However, in a cohort of metastatic breast cancer patients who received tamoxifen treatment, high BCAR3 mRNA levels were associated with favorable progression-free survival outcome...
2014: Breast Cancer Research: BCR
Mi-Sun Lim, Kwang Won Jeong
Flightless-I (Drosophila) homolog (FLII) is a nuclear receptor coactivator that is known to interact with other transcriptional regulators such as the SWI/SNF complex, an ATP-dependent chromatin-remodeling complex, at the promoter or enhancer region of estrogen receptor (ER)-α target genes. However, little is known about the role of FLII during transcription initiation in the transforming growth factor beta (TGFβ)/SMAD-dependent signaling pathway. Here, we demonstrate that FLII functions as a coactivator in the expression of type I collagen gene induced by TGFβ in A549 cells...
November 21, 2014: Biochemical and Biophysical Research Communications
Dal Kim, Ae Sin Lee, Yu Jin Jung, Kyoung Hee Yang, Sik Lee, Sung Kwang Park, Won Kim, Kyung Pyo Kang
BACKGROUND: After insult to the kidney, a renal fibrotic process is initiated with sustained inflammation, fibroblast activation and accumulation of extracellular matrix (ECM). Tamoxifen has been used as an anti-estrogen for the prevention and treatment of breast cancer. In this study, we investigated the protective effects of tamoxifen on unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis and its molecular mechanism. METHODS: Renal fibrosis was induced by UUO in 7-week-old C57BL/6 mice...
November 2014: Nephrology, Dialysis, Transplantation
Miriam Güemes, Alejandro J Garcia, Diana Rigueur, Stephanie Runke, Weiguang Wang, Gexin Zhao, Victor Hugo Mayorga, Elisa Atti, Sotirios Tetradis, Bruno Péault, Karen Lyons, Gustavo A Miranda-Carboni, Susan A Krum
Osteoporosis is a disease characterized by low bone mass, leading to an increased risk of fragility fractures. GATA4 is a zinc-finger transcription factor that is important in several tissues, such as the heart and intestines, and has recently been shown to be a pioneer factor for estrogen receptor alpha (ERα) in osteoblast-like cells. Herein, we demonstrate that GATA4 is necessary for estrogen-mediated transcription and estrogen-independent mineralization in vitro. In vivo deletion of GATA4, driven by Cre-recombinase in osteoblasts, results in perinatal lethality, decreased trabecular bone properties, and abnormal bone development...
December 2014: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Hye-Rim Lee, Kyung-A Hwang, Kyung-Chul Choi
The distinct roles of estrogen receptors (ERs) related with androgen receptors (ARs) have been proposed in prostate cancer, while the involvement of transforming growth factor-β (TGF-β) has been reported in the progression of prostate cancer. In this study, we examined whether the TGF-β signaling pathway is associated with ER signaling in LNCaP prostate cancer cells, which express ERα, ERβ and ARs. We determined whether the exposure to phthalates may induce prostate cancer progression by affecting molecular crosstalk between ER and TGF-β signaling pathways...
August 2014: International Journal of Oncology
Yi-Chen Li, Xuan-Sheng Ding, Hui-Mei Li, Ying Zhang, Jing Bao
Estrogen has been demonstrated to exert beneficial effects on kidney; however, the role of G protein-coupled estrogen receptor 1 (GPER) is still uncertain. In the present study, we investigated the effect of 17β-estradiol and GPER agonist Fulvestrant on extracellular matrix production under transforming growth factor-β1 (TGF-β1) stimulation in human and rat mesangial cells. As a result, 17β-estradiol and Fulvestrant inhibit TGF-β1-induced type IV collagen and fibronectin expression in a dose-dependent manner, by suppressing acute Smad2/3 phosphorylation and Smad4 complex formation...
June 25, 2014: Molecular and Cellular Endocrinology
Natsuka Goto, Hiromi Hiyoshi, Ichiaki Ito, Keisuke Iida, Yuka Nakajima, Kazuo Nagasawa, Junn Yanagisawa
Breast cancer is the most frequently diagnosed cancer and the leading cause of death by cancer among females worldwide. An overwhelming majority of these deaths is because of metastasis. Estrogen stimulates and promotes growth of breast tumors, whereas transforming growth factor-beta (TGF-β) signaling promotes invasion and metastasis. We previously reported that estrogen and estrogen receptor alpha (ERα) suppressed breast cancer metastasis by inhibiting TGF-β signaling, whereas antiestrogens that suppress breast cancer growth, such as the selective ER modulator tamoxifen (TAM) or the pure antiestrogen fulvestrant (ICI 182,780), cannot suppress TGF-β signaling or breast cancer invasiveness...
2014: Journal of Cancer
Michael Dews, Grace S Tan, Stacy Hultine, Pichai Raman, Jaewoo Choi, Elizabeth K Duperret, Jack Lawler, Adam Bass, Andrei Thomas-Tikhonenko
BACKGROUND: The c-Myc oncoprotein is activated in the majority of colorectal cancers (CRCs), whereas the TGF-β pathway is frequently affected by loss-of-function mutations, for example in SMAD2/3/4 genes. The canonical model places Myc downstream of inhibitory TGF-β signaling. However, we previously demonstrated that Myc also inhibits TGF-β signaling through the miR-17~92 microRNA cluster, raising the question about functional relationships between these two pathways. METHODS: We engineered a series of genetically complex murine and human CRC cell lines in which Myc and TGF-β activities could be manipulated simultaneously...
April 2014: Journal of the National Cancer Institute
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