scholarly journals Estrogen signaling in the proliferative endometrium: implications in endometriosis

2016 ◽  
Vol 62 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Rita de Cássia Pereira da Costa e Silva ◽  
Kátia Karina Verolli de Oliveira Moura ◽  
Circoncisto Laurentino Ribeiro Júnior ◽  
Lidia Andreu Guillo
Keyword(s):  
Signaling Pathways ◽  
Physiological Role ◽  
Estrogen Signaling ◽  
Normal Endometrium ◽  
Cell Culture Techniques ◽  
Culture Techniques ◽  
Endometrial Cells ◽  
Signaling Mechanisms ◽  
Proliferative Endometrium

SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

scholarly journals Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Da Huang ◽  
Jiayu Shen ◽  
Lingyun Zhai ◽  
Huanhuan Chen ◽  
Jing Fei ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Tumor Immunity ◽  
Malignant Tumors ◽  
Physiological Role ◽  
Cancer Cell Line ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

N-Acylethanolamine Acid Amidase (NAAA) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of NAAA was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

scholarly journals Immunohistochemical Expression of Retinoblastoma Gene Product in Normal, Hyperplastic and Malignant Endometrium. Correlation with p53 Protein Expression, c-erbB-2, Hormone Receptors’ Status and Proliferative Activity

2002 ◽  
Vol 18 (3) ◽  
pp. 143-152 ◽  
Author(s):  
E. E. Ioachim ◽  
A. C. Goussia ◽  
E. G. Kitsiou ◽  
K. Charalabopoulos ◽  
E. Mermiga ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hormone Receptors ◽  
P53 Protein ◽  
Growth Fraction ◽  
Normal Endometrium ◽  
Endometrial Cells ◽  
Proliferative Growth ◽  
Proliferative Endometrium ◽  
Endometrial Carcinomas ◽  
Secretory Endometrium

Alterations of the retinoblastoma (Rb) gene have been described in several human neoplasms and recently, it has been suggested that these alterations may play a role in the development of endometrial carcinomas. Paraffin sections from 31 cases of normal endometrium (16 proliferative, 15 secretory), 35 hyperplastic lesions and 89 endometrial carcinomas were investigated immunohistochemically for Rb protein (pRb) expression. The results were compared with p53 and c-erbB-2 protein expression, estrogen (ER) and progesterone (PR) receptors’ status and with clinicopathological prognostic factors. pRb was expressed in normal, hyperplastic and neoplastic epithelium. Proliferative endometrium showed more intense and extensive pRb staining than secretory endometrium. pRb reactivity was heterogeneous in the hyperplastic endometrial cells. Lack or focal (< 10% of endometrial cells) pRb immunostaining was noted in 56.2% and 27% of carcinomas, respectively. In the remaining cases (16.8%) pRb staining was heterogeneous or diffuse. The absence or presence of pRb expression was independent of grade and stage. In normal proliferative and secretory endometrium, pRb expression was correlated with PR (p= 0.006 andp= 0.001, respectively), PCNA (p= 0.04 andp= 0.01, respectively) and MIB1 (p= 0.02 and p < 0.0001, respectively) expression. In hyperplasias, pRb was related to PR (p= 0.016) and MIB1 (p< 0.0001) expression. In carcinomas, a relationship of pRb expression with p53 (p= 0.0015), ER (p= 0.0002), PR (p= 0.0004) and PCNA (p= 0.013) status was detected. We suggest that the absence or presence of pRb expression does not seem to be associated with the progression of endometrioid carcinoma. In addition, pRb seems to be normally regulated in relation to the proliferative growth fraction of the tumours.

scholarly journals NF-κB—An Important Player in Xenoestrogen Signaling in Immune Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1799
Author(s):  
Karolina Nowak ◽  
Ewa Jabłońska ◽  
Wioletta Ratajczak-Wrona
Keyword(s):  
Immune System ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Estrogen Signaling ◽  
Cellular Processes ◽  
Pathogenic Factors ◽  
Important Player ◽  
Exogenous Factors

The proper functioning of the immune system is critical for an effective defense against pathogenic factors such as bacteria and viruses. All the cellular processes taking place in an organism are strictly regulated by an intracellular network of signaling pathways. In the case of immune cells, the NF-κB pathway is considered the key signaling pathway as it regulates the expression of more than 200 genes. The transcription factor NF-κB is sensitive to exogenous factors, such as xenoestrogens (XEs), which are compounds mimicking the action of endogenous estrogens and are widely distributed in the environment. Moreover, XE-induced modulation of signaling pathways may be crucial for the proper development of the immune system. In this review, we summarize the effects of XEs on the NF-κB signaling pathway. Based on our analysis, we constructed a model of XE-induced signaling in immune cells and found that in most cases XEs activate NF-κB. Our analysis indicated that the indirect impact of XEs on NF-κB in immune cells is related to the modulation of estrogen signaling and other pathways such as MAPK and JAK/STAT. We also summarize the role of these aspects of signaling in the development and further functioning of the immune system in this paper.

scholarly journals Single-Chain Estrogen Receptors (ERs) Reveal that the ERα/β Heterodimer Emulates Functions of the ERα Dimer in Genomic Estrogen Signaling Pathways

2004 ◽  
Vol 24 (17) ◽  
pp. 7681-7694 ◽  
Author(s):  
Xiaodong Li ◽  
Jing Huang ◽  
Ping Yi ◽  
Robert A. Bambara ◽  
Russell Hilf ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Mammalian Cells ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Single Chain ◽  
Estrogen Responsive Element ◽  
17Β Estradiol ◽  
Responsive Element

ABSTRACT The effects of estrogens, particularly 17β-estradiol (E2), are mediated by estrogen receptor α (ERα) and ERβ. Upon binding to E2, ERs homo- and heterodimerize when coexpressed. The ER dimer then regulates the transcription of target genes through estrogen responsive element (ERE)-dependent and -independent pathways that constitute genomic estrogen signaling. Although ERα and ERβ have similar ERE and E2 binding properties, they display different transregulatory capacities in both ERE-dependent and -independent signaling pathways. It is therefore likely that the heterodimerization provides novel functions to ERs by combining distinct properties of the contributing partners. The elucidation of the role of the ER heterodimer is critical for the understanding of physiology and pathophysiology of E2 signaling. However, differentially determining target gene responses during cosynthesis of ER subtypes is difficult, since dimers formed are a heterogeneous population of homo- and heterodimers. To circumvent the pivotal dimerization step in ER action and hence produce a homogeneous ER heterodimer population, we utilized a genetic fusion strategy. We joined the cDNAs of ERα and/or ERβ to produce single-chain ERs to simulate the ER homo- and heterodimers. The fusion ERs interacted with ERE and E2 in a manner similar to that observed with the ER dimers. The homofusion receptors mimicked the functions of the parent ER dimers in the ERE-dependent and -independent pathways in transfected mammalian cells, whereas heterofusion receptors emulated the transregulatory properties of the ERα dimer. These results suggest that ERα is the functionally dominant partner in the ERα/β heterodimer.

scholarly journals Expression of corticotrophin-releasing hormone in the mouse uterus: participation in embryo implantation

1999 ◽  
Vol 163 (2) ◽  
pp. 221-227 ◽  
Author(s):  
I Athanassakis ◽  
V Farmakiotis ◽  
I Aifantis ◽  
A Gravanis ◽  
S Vassiliadis
Keyword(s):  
Cell Culture ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
Pregnant Uterus ◽  
Cell Culture Techniques ◽  
Releasing Hormone ◽  
Culture Techniques ◽  
Blastocyst Implantation ◽  
Implantation Sites

The detection of corticotropin-releasing hormone (CRH) in the pregnant and non-pregnant uterus has driven research to determine the role of this 41 amino acid neuropeptide in the female reproductive system. As concentrations of CRH mRNA and its peptide product are greater in the implantation sites of the early pregnant uterus compared with the regions between implantation sites, CRH has been hypothesised to participate in blastocyst implantation. Using the mouse system as an experimental model, we studied the distribution of CRH in the uterus during the oestrus cycle and early gestational period, and now provide evidence for its involvement in embryo implantation using cell culture techniques. The percentage of CRH-positive uterine cells and the amount of CRH released during anoestrus, pro-oestrus and oestrus were determined by immunofluorescence and ELISA experiments respectively. The highest number of intracellularly CRH-positive cells was obtained during pro-oestrus, whereas the highest CRH concentration in uterine cell culture supernatants was detected during anoestrus. At early stages of gestation, CRH was detected in the endometrium on days 2, 3 and 4 of pregnancy and in the myometrium on days 3 and 4, whereas it was undetectable on day 5. The functional role of CRH during early gestation was evaluated by administering anti-CRH antibody to mice from day 3 to day 8 of pregnancy. This treatment resulted in implantation failure in 60% of the cases, in which implantation sites, although clearly present in the uterus, had failed to host an embryo. These results provide direct evidence about the involvement of CRH in murine embryo implantation and are in agreement with hypotheses postulated in humans.

scholarly journals Signaling pathways regulating Homer1a expression: implications for antidepressant therapy

2016 ◽  
Vol 397 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Tsvetan Serchov ◽  
Rolf Heumann ◽  
Dietrich van Calker ◽  
Knut Biber
Keyword(s):  
Signaling Pathways ◽  
Potential Role ◽  
Current Knowledge ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Antidepressant Therapy ◽  
Pharmacological Treatments ◽  
Signaling Mechanisms

Abstract Homer1a is upregulated by several different antidepressant measures, including non-pharmacological treatments, like sleep deprivation (SD) and electroconvulsive therapy (ECT) and antidepressant drugs, such as imipramine, fluoxetine and ketamine. Homer1a induction might thus be a crucial joint mechanism for antidepressant therapy in general. However, the upstream signaling pathways that regulate or induce Homer1a expression are still not well understood. The main focus of the present review is to offer an overview of the current knowledge about the potential role of Homer1a in depression and the signaling pathways responsible for Homer1a regulation. It is suggested here that a detailed characterization of the signaling mechanisms leading to Homer1a expression might provide novel therapeutic targets for antidepressant drug development.

A T.E.M. study of mouse mammary epithelial cell secretory differentiation cultured on collagen and Matrigel

1991 ◽  
Vol 49 ◽  
pp. 188-189
Author(s):  
W.N. Bentham ◽  
V. Rocha
Keyword(s):  
Cell Culture ◽  
Mammary Epithelial ◽  
Secretory Process ◽  
Cell Culture System ◽  
Protein Maturation ◽  
Cell Culture Techniques ◽  
Culture Techniques ◽  
Mouse Mammary Epithelial Cell ◽  
Secretory Differentiation

It has been an interest of our lab to develop a mammary epethelial cell culture system that faithfully duplicates the in vivo condition of the lactating gland. Since the introduction of collagen as a matrix on which cells are cultivated other E.C.M. type matrices have been made available and are used in many cell culture techniques. We have previously demonstrated that cells cultured on collagen and Matrigel do not differentiate as they do in vivo. It seems that these cultures often produce cells that show a disruption in the secretory process. The appearance of large ribosomal studded vesicles, that specifically label with antibody to casein, suggest an interruption of both protein maturation and secretion at the E.R. to golgi transition. In this report we have examined cultures on collagen and Matrigel at relative high and low seeding densities and compared them to cells from the in vivo condition.

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