Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Estrogen receptors (ER) α and β are found in both women and men in many tissues, where they have different functions, including having roles in cell proliferation and differentiation of the reproductive tract. In addition to estradiol (E2), a natural hormone, numerous compounds are able to bind ERs and modulate their activities. Among these compounds, phytoestrogens such as isoflavones, which are found in plants, are promising therapeutics for several pathologies. Glyceollins are second metabolites of isoflavones that are mainly produced in soybean in response to an elicitor. They have potentially therapeutic actions in breast cancer by reducing the proliferation of cancer cells. However, the molecular mechanisms driving these effects remain elusive. METHODS: First, to determine the proliferative or anti-proliferative effects of glyceollins, in vivo and in vitro approaches were used. The length of epithelial duct in mammary gland as well as uterotrophy after treatment by E2 and glyceollins and their effect on proliferation of different breast cell line were assessed. Secondly, the ability of glyceollin to activate ER was assessed by luciferase assay. Finally, to unravel molecular mechanisms involved by glyceollins, transcriptomic analysis was performed on MCF-7 breast cancer cells. RESULTS: In this study, we show that synthetic versions of glyceollin I and II exert anti-proliferative effects in vivo in mouse mammary glands and in vitro in different ER-positive and ER-negative breast cell lines. Using transcriptomic analysis, we produce for the first time an integrated view of gene regulation in response to glyceollins and reveal that these phytochemicals act through at least two major pathways. One pathway involving FOXM1 and ERα is directly linked to proliferation. The other involves the HIF family and reveals that stress is a potential factor in the anti-proliferative effects of glyceollins due to its role in increasing the expression of REDD1, an mTORC1 inhibitor. CONCLUSION: Overall, our study clearly shows that glyceollins exert anti-proliferative effects by reducing the expression of genes encoding cell cycle and mitosis-associated factors and biomarkers overexpressed in cancers and by increasing the expression of growth arrest-related genes. These results reinforce the therapeutic potential of glyceollins for breast cancer.
ISSN: 1478-811X

hal-01560288
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560288
DOI : 10.1186/s12964-017-0182-1
PUBMED : 28666461

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
In mammals, the effects of estrogen are mainly mediated by two different estrogen receptors, ERα and ERβ. These proteins are members of the nuclear receptor family, characterized by distinct structural and functional domains, and participate in the regulation of different biological processes, including cell growth, survival and differentiation. The two estrogen receptor (ER) subtypes are generated from two distinct genes and have partially distinct expression patterns. Their activities are modulated differently by a range of natural and synthetic ligands. Some of these ligands show agonistic or antagonistic effects depending on ER subtype and are described as selective ER modulators (SERMs). Accordingly, a few phytochemicals, called phytoestrogens, which are synthesized from plants and vegetables, show low estrogenic activity or anti-estrogenic activity with potentially anti-proliferative effects that offer nutraceutical or pharmacological advantages. These compounds may be used as hormonal substitutes or as complements in breast cancer treatments. In this review, we discuss and summarize the in vitro and in vivo effects of certain phytoestrogens and their potential roles in the interaction with estrogen receptors.
ISSN: 1422-0067

hal-01560283
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560283
PUBMED : 28657580
DOI : 10.3390/ijms18071381

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Xeno-estrogens, a class of endocrine disrupting chemicals (EDCs), can disturb estrogen receptor-dependent pathways involved in differentiation, proliferation or protection. Multiple methods have been developed to characterize the disturbances induced by EDCs in different cells or organs. In this study we have developed a new tool for the assessment of estrogenic compounds on differentiation. For this purpose we used the global model of NGF-induced neurite outgrowth of a pseudoneuronal PC12 cell line stably transfected with estrogen receptor alpha (PC12 ER). This new test evidences a new selectivity in which estradiol, genistein and 4-hydroxytamoxifen increased the NGF-induced neurite outgrowth of PC12 ER cells in a dose-dependent manner. In contrast, the strong estrogen agonist 17α-ethynylestradiol, the strong antagonist raloxifene and the agonist bisphenol A were unable to modify the neuritogenesis of PC12 ER cells. Therefore, the analysis of neuritogenesis in PC12 ER cells constitutes a complementary tool for the characterization of xeno-estrogen activity and also serves as a basis for further studies focusing on the mechanisms of EDCs in a neuronal context. Moreover, this test constitutes an alternative to animal testing.
ISSN: 0045-6535

hal-01063907
https://hal.archives-ouvertes.fr/hal-01063907
https://hal.archives-ouvertes.fr/hal-01063907/document
https://hal.archives-ouvertes.fr/hal-01063907/file/Differentiationsur PC12_cells_accepted.pdf
DOI : 10.1016/j.chemosphere.2014.03.101

Éditeur(s) : HAL CCSD
Résumé : International audience
A mode stirred reverberation chamber (RC) is designed to conduct in vivo studies in the 60-GHz band. This exposure system has suitable features for experiments on animals. An interface, for temperature measurements using an infrared (IR) camera, is designed in the chamber wall in order to measure the specific absorption rate and/or the power density inside the chamber.
BIOEM 2016
Gand, Belgium

hal-01377564
https://hal.archives-ouvertes.fr/hal-01377564
https://hal.archives-ouvertes.fr/hal-01377564/document
https://hal.archives-ouvertes.fr/hal-01377564/file/bioem%202016_2_final.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Many studies have reported proliferative, differentiating or protective effects of estradiol, notably through estrogen receptor alpha (ERα). On the contrary, the ligand-independent action of ERα is currently poorly documented notably in cell protection. The stable transfection of wild type, substituted or truncated form of ERα in PC12 cells (ERα negative cell line) lead the specific study of its ligand-independent action. Hence, we demonstrate here that, in the absence of E2, the expression of ERα prevents cells from apoptosis induced by serum deprivation. This protection is not due to an ERE-mediated transcription and does not require either AF-1 or AF-2 transactivation functions. It is afforded to the Y537 residue of ERα and activation of c-Src/Stat3 signaling pathway.
ISSN: 1932-6203

inserm-00865332
http://www.hal.inserm.fr/inserm-00865332
http://www.hal.inserm.fr/inserm-00865332/document
http://www.hal.inserm.fr/inserm-00865332/file/PMID_23825704.pdf
DOI : 10.1371/journal.pone.0069081

Éditeur(s) : HAL CCSD
Résumé : International audience
BIOEM
Hangzhou, China

hal-01627606
https://hal.archives-ouvertes.fr/hal-01627606

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
ISSN: 1757-4676

hal-01118028
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118028
PUBMED : 25214462
PUBMEDCENTRAL : PMC4287935
DOI : 10.15252/emmm.201404112