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https://www.readbyqxmd.com/read/28610679/the-presence-of-a-membrane-bound-progesterone-receptor-induces-growth-of-breast-cancer-with-norethisterone-but-not-with-progesterone-a-xenograft-model
#1
Yue Zhao, Xiangyan Ruan, Husheng Wang, Xue Li, Muqing Gu, Lijuan Wang, Yanglu Li, Harald Seeger, Alfred O Mueck
OBJECTIVES: During menopausal hormone therapy (MHT) a possible increase in breast cancer risk is thought to depend mainly on the progestogen component. In vitro studies have shown that the progesterone receptor membrane component 1 (PGRMC1) is important for tumor proliferation induced by progestogens. The primary aim of this study was to compare for the first time the natural progestogen, progesterone (P), with a synthetic progestogen, norethisterone (NET), using a xenograft model. METHODS: MCF7 cells, transfected with PGRMC1 plasmid or empty vector, were injected into nude mice and estradiol (E2) pellets were implanted...
August 2017: Maturitas
https://www.readbyqxmd.com/read/28493650/pro-survival-redox-signalling-in-progesterone-mediated-retinal-neuroprotection
#2
Ana M Ruiz Lopez, Sarah L Roche, Alice C Wyse Jackson, Jennifer N Moloney, Ashleigh M Byrne, Thomas G Cotter
Retinitis pigmentosa (RP) is a group of hereditary retinal diseases, characterised by photoreceptor cell loss. Despite a substantial understanding of the mechanisms leading to cell death, an effective therapeutic strategy is sought. Our laboratory has previously demonstrated the neuroprotective properties of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other retinal studies, we have also presented a pro-survival role for reactive oxygen species (ROS), downstream of bFGF...
May 11, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28488575/proteomics-analysis-of-bladder-cancer-invasion-targeting-eif3d-for-therapeutic-intervention
#3
Agnieszka Latosinska, Marika Mokou, Manousos Makridakis, William Mullen, Jerome Zoidakis, Vasiliki Lygirou, Maria Frantzi, Ioannis Katafigiotis, Konstantinos Stravodimos, Marie C Hupe, Maciej Dobrzynski, Walter Kolch, Axel S Merseburger, Harald Mischak, Maria G Roubelakis, Antonia Vlahou
Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396637/membrane-associated-progesterone-receptors-promiscuous-proteins-with-pleiotropic-functions-focus-on-interactions-with-cytochromes-p450
#4
REVIEW
Chang S Ryu, Kathrin Klein, Ulrich M Zanger
Membrane-associated progesterone receptors (MAPR) are a group of four rather small, partially homologous proteins, which share a similar non-covalent heme-binding domain that is related to cytochrome b5, a well-known functional interaction partner of microsomal cytochrome P450 (CYP) monooxygenase systems. Apart from their structural similarities the four proteins progesterone membrane component 1 (PGRMC1, also referred to as IZA, sigma-2 receptor, Dap1), PGRMC2, neudesin (NENF) and neuferricin (CYB5D2) display surprisingly divergent and multifunctional physiological properties related to cholesterol/steroid biosynthesis, drug metabolism and response, iron homeostasis, heme trafficking, energy metabolism, autophagy, apoptosis, cell cycle regulation, cell migration, neural functions, and tumorigenesis and cancer progression...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28388727/progesterone-receptors-and-proliferation-of-the-endometrium-in-obese-women-with-polycystic-ovary-syndrome-a-lifestyle-intervention-study
#5
Mariana Paulson, Lena Sahlin, Angelica Lindén Hirschberg
Context: Polycystic ovary syndrome (PCOS) is associated with increased risk of endometrial cancer. This is usually explained by chronic anovulation and deficient progesterone activity. However, the role of progesterone receptors (PRs) in endometrial proliferation is unclear. Objective: To evaluate PRs in relation to endometrial proliferation in women with PCOS. Design: Cross-sectional study and lifestyle intervention. Setting: Clinical and laboratory research unit at a university hospital...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28371915/ag-205-a-progesterone-receptor-membrane-component-1-antagonist-ablates-progesterone-s-ability-to-block-oxidative-stress-induced-apoptosis-of-human-granulosa-luteal-cells%C3%A2
#6
Erica Anspach Will, Xiufang Liu, John J Peluso
The present studies were designed to determine whether progesterone (P4)-progesterone receptor membrane component 1 (PGRMC1) signaling is able to attenuate the apoptotic effects of oxidative stress induced by hydrogen peroxide (H2O2). To achieve this goal, freshly isolated human granulosa/luteal cells were maintained in culture. After several passages, the cells were treated with H2O2, which induced apoptosis within 2.5 h, while simultaneous treatment with P4 attenuated the apoptotic action of H2O2. AG 205, a PGRMC1 antagonist, eliminated P4's ability to prevent H2O2-induced apoptosis...
April 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28321005/the-concentration-dependent-effect-of-progesterone-on-follicle-growth-in-the-mouse-ovary
#7
Kouji Komatsu, Satoru Masubuchi
Follicle growth in the mammalian ovary is coordinately controlled by multiple factors to sustain periodic ovulation. In this study, we investigated the role of progesterone on follicle growth in the mouse ovary. As the concentration of progesterone changes during the estrus cycle, we cultured the sliced mouse ovary in a medium containing 10 ng/ml, 100 ng/ml, and 1 μg/ml progesterone. Progesterone promoted the growth of primordial to primary follicles at 100 ng/ml, while it suppressed the growth of secondary follicles at 1 μg/ml...
March 17, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28250339/the-evolutionary-appearance-of-signaling-motifs-in-pgrmc1
#8
Michael A Cahill
A complex PGRMC1-centred regulatory system controls multiple cell functions. Although PGRMC1 is phosphorylated at several positions, we do not understand the mechanisms regulating its function. PGRMC1 is the archetypal member of the membrane associated progesterone receptor (MAPR) family. Phylogentic comparison of MAPR proteins suggests that the ancestral metazoan "PGRMC-like" MAPR gene resembled PGRMC1/PGRMC2, containing the equivalents of PGRMC1 Y139 and Y180 SH2 target motifs. It later acquired a CK2 site with phosphoacceptor at S181...
February 28, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28197632/pgrmc1-dependent-autophagy-by-hyperoside-induces-apoptosis-and-sensitizes-ovarian-cancer-cells-to-cisplatin-treatment
#9
Xiaofei Zhu, Mingde Ji, Yue Han, Yuanyuan Guo, Wenqiang Zhu, Feng Gao, Xuewen Yang, Chunbing Zhang
Cisplatin treatment some times leads to chemoresistance, which is now acknowledged partially due to the inductive expression of progesterone receptor membrane component (PGRMC)1 in ovarian cancer cells. PGRMC1 enhances autophagy, activates cytochrome p450, and inveigles signaling pathways to promote cell survival and reduce the effect of drug treatments. In this study, we give first line evidence that hyperoside inhibits cell viability, triggers autophagy and apoptosis in ovarian cancer cell lines. Mechanistically, PGRMC1-dependent autophagy was utilized by hyperoside to induce apoptotic cell death...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28120522/sigma-2-receptor-expression-levels-in-blood-and-bladder-from-healthy-and-bladder-cancer-cattle
#10
V Russo, C Inglese, L Avallone, F Roperto, C Abate, N Zizzo, J S Munday, F Berardi, N A Colabufo, S Roperto
The expression of sigma-2 receptor (S2R) was assayed in blood and bladder samples from healthy cattle and in blood and bladder of cattle with deltapapillomavirus-associated urothelial tumors. Samples of bladder from cattle with neoplasia had significantly higher S2R than samples of bladder from healthy cattle (95% CI 0.31-0.82, P < 0.05). In addition, significantly higher S2R was detected in the blood of cattle with bladder cancer than blood from healthy cattle (95% CI 0.22-0.41, P < 0.05). The results provide evidence that increased expression of SR2 in blood could be useful as circulating biomarker for bladder cancer in cattle...
January 25, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28117714/tissue-non-specific-genes-and-pathways-associated-with-diabetes-an-expression-meta-analysis
#11
Hao Mei, Lianna Li, Shijian Liu, Fan Jiang, Michael Griswold, Thomas Mosley
We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets...
January 21, 2017: Genes
https://www.readbyqxmd.com/read/28107520/pgrmc1-is-a-novel-potential-tumor-biomarker-of-human-renal-cell-carcinoma-based-on-quantitative-proteomic-and-integrative-biological-assessments
#12
Dan Zhang, Xiangying Xia, Xixi Wang, Peng Zhang, Weiliang Lu, Yamei Yu, Shi Deng, Hanshuo Yang, Hongxia Zhu, Ningzhi Xu, Shufang Liang
Progesterone receptor membrane component 1 (PGRMC1) is widely observed with an elevated level in multiple human cancers. However, the roles of PGRMC1 in renal cancer are not clear and merit further study. In this report, we made a systematic, integrative biological assessment for PGRMC1 in renal cell carcinoma (RCC) by a quantitative proteomic identification, immunohistochemical detection, and its clinic pathologic significance analysis. We found that PGRMC1 abundance is increased by 3.91-fold in RCC tissues compared with its autologous para-cancerous tissues by a quantitative proteome identification...
2017: PloS One
https://www.readbyqxmd.com/read/28104494/thoughts-on-interactions-between-pgrmc1-and-diverse-attested-and-potential-hydrophobic-ligands
#13
REVIEW
Michael A Cahill, Amy E Medlock
Progesterone Receptor Membrane Component 1 (PGRMC1) is located in many different subcellular locations with many different attested and probably location-specific functions. PGRMC1 was recently identified in the mitochondrial outer membrane where it interacts with ferrochelatase, the last enzyme in the heme synthetic pathway. It has been proposed that PGRMC1 may act as a chaperone to shuttle newly synthesized heme from the mitochondrion to cytochrome P450 (cyP450) enzymes. Here we consider potential roles that PGRMC1 may play in transferring heme, and other small hydrophobic ligands such as cholesterol and steroids, between the hydrophobic compartment of the membrane lipid bilayer interior to aqueous proteins, and perhaps to the membranes of other organelles...
January 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28007569/sigma-2-receptor-and-progesterone-receptor-membrane-component-1-pgrmc1-are-two-different-proteins-proofs-by-fluorescent-labeling-and-binding-of-sigma-2-receptor-ligands-to-pgrmc1
#14
Maria Laura Pati, Diana Groza, Chiara Riganti, Joanna Kopecka, Mauro Niso, Francesco Berardi, Sonja Hager, Petra Heffeter, Miwa Hirai, Hitoshi Tsugawa, Yasuaki Kabe, Makoto Suematsu, Carmen Abate
A controversial relationship between sigma-2 and progesterone receptor membrane component 1 (PGRMC1) proteins, both representing promising targets for the therapy and diagnosis of tumors, exists since 2011, when the sigma-2 receptor was reported to be identical to PGRMC1. Because a misidentification of these proteins will lead to biased future research hampering the possible diagnostic and therapeutic exploitation of the two targets, there is the need to solve the debate on their identity. With this aim, we have herein investigated uptake and distribution of structurally different fluorescent sigma-2 receptor ligands by flow cytometry and confocal microscopy in MCF7 cells, where together with intrinsic sigma-2 receptors, PGRMC1 was constitutively present or alternatively silenced or overexpressed...
December 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28007532/role-of-g-protein-coupled-estrogen-receptor-gper-gpr30-in-maintenance-of-meiotic-arrest-in-fish-oocytes
#15
REVIEW
Peter Thomas
An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E2) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (Gs) on oocyte plasma membranes resulting in stimulation of cAMP production and maintenance of elevated cAMP levels...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28005395/conditional-ablation-of-progesterone-receptor-membrane-component-2-causes-female-premature-reproductive-senescence
#16
Nicole C Clark, Cindy A Pru, Siu-Pok Yee, John P Lydon, John J Peluso, James K Pru
The nonclassical progesterone receptors progesterone receptor membrane component (PGRMC) 1 and PGRMC2 have been implicated in regulating cell survival of endometrial and ovarian cells in vitro and are abundantly expressed in these cell types. The objective of this study was to determine if Pgrmc1 and Pgrmc2 are essential for normal female reproduction. To accomplish this objective, Pgrmc1 and/or Pgrmc2 floxed mice (Pgrmc2fl/fl and Pgrmc1/2fl/fl) were crossed with Pgr-cre mice, which resulted in the conditional ablation of Pgrmc1 and/or Pgrmc2 from female reproductive tissues (i...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/27997272/progesterone-receptors-and-proliferation-of-the-endometrium-in-obese-women-with-polycystic-ovary-syndrome-a-lifestyle-intervention-study
#17
M Paulson, L Sahlin, A L Hirschberg
CONTEXT: Polycystic ovary syndrome (PCOS) is associated with increased risk of endometrial cancer. This is usually explained by chronic anovulation and deficient progesterone activity. However, the role of progesterone receptors (PRs) in endometrial proliferation is unclear. OBJECTIVE: To evaluate PRs in relation to endometrial proliferation in women with PCOS. DESIGN: Cross-sectional study and lifestyle intervention. SETTINGS: Clinical and laboratory research unit at a university hospital...
December 20, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuroinflammation-in-experimental-models-of-alzheimer-s-disease
#18
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa L Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan T Pierce, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R ligands SAS-0132 and JVW-1009 are neuroprotective in a C. elegans model of amyloid precursor protein-mediated neurodegeneration...
February 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27859822/expression-of-steroidogenic-enzymes-and-steroid-receptors-in-foetal-gonads-of-domestic-cat-sex-similarities-and-differences
#19
B C Braun, K Jewgenow
Foetal gonads already produce steroid hormones and by this influence the further development of external and internal genitalia as well as of the brain. Beside this, foetal gonads themselves can be influenced by foetal or maternal hormones. The time course of foetal gonadal development can differ between species. As knowledge on processes in domestic cats is very limited, the steroidogenic enzyme expressions as well as these of steroid receptors were analysed in foetal gonads of domestic cats. We investigated a period from beginning of the second half of pregnancy to the beginning of the third trimester; a phase, where also gonadal development proceeds...
November 15, 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27848973/progesterone-receptor-membrane-component-1-mediates-progesterone-induced-suppression-of-oocyte-meiotic-prophase-i-and-primordial-folliculogenesis
#20
Meng Guo, Cheng Zhang, Yan Wang, Lizhao Feng, Zhengpin Wang, Wanbo Niu, Xiaoyan Du, Wang Tang, Yuna Li, Chao Wang, Zhenwen Chen
Well-timed progression of primordial folliculogenesis is essential for mammalian female fertility. Progesterone (P4) inhibits primordial follicle formation under physiological conditions; however, P4 receptor that mediates this effect and its underlying mechanisms are unclear. In this study, we used an in vitro organ culture system to show that progesterone receptor membrane component 1 (PGRMC1) mediated P4-induced inhibition of oocyte meiotic prophase I and primordial follicle formation. We found that membrane-impermeable BSA-conjugated P4 inhibited primordial follicle formation similar to that by P4...
November 16, 2016: Scientific Reports
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