scholarly journals Control of Endothelin-A Receptor Expression by Progesterone Is Enhanced by Synergy With Gata2

2013 ◽  
Vol 27 (6) ◽  
pp. 892-908 ◽  
Author(s):  
Yanping Zhang ◽  
Gregory R. Knutsen ◽  
Matthew D. Brown ◽  
L. Bruno Ruest
Keyword(s):  
Progesterone Receptor ◽  
Gene Activation ◽  
Neural Crest Cell ◽  
Receptor Expression ◽  
Endothelin A Receptor ◽  
Endothelin A ◽  
Progesterone Receptor B ◽  
Crest Cell

Abstract The endothelin-A receptor (Ednra) is involved in several physiological, pathological, and developmental pathways. Known for its function in vasoconstriction after being activated by endothelin-1, Ednra also controls cephalic neural crest cell development and appears to play a role in several pathologies, including cancer and periodontitis. However, the mechanisms regulating Ednra expression have not been identified despite its important functions. In this study, we investigated the role progesterone plays in Ednra gene expression in vivo and in vitro. In mice, pregnancy promotes Ednra expression in the heart, kidney, lung, uterus, and placenta, and the up-regulation is mediated by progesterone. We determined that the conserved region between −5.7 and −4.2 kb upstream of the mouse Ednra gene is necessary for the progesterone response. We also found that progesterone mediates Ednra activation through progesterone receptor B activation by its recruitment to PRE6, one of the 6 progesterone response elements found in that locus. However, gene activation by means of a GATA2 site was also necessary for the progesterone response. The Gata2 transcription factor enhances the progesterone response mediated by the progesterone receptor B. Together these results indicate that progesterone regulates Ednra expression by synergizing with Gata2 activity, a previously unknown mechanism. This mechanism may have an impact on pathologies involving the endothelin signaling.

Role of endothelin a receptor in colon cancer metastasis: In vitro and in vivo evidence

2013 ◽  
Vol 53 (S1) ◽  
pp. E85-E91 ◽  
Author(s):  
Shaolin Nie ◽  
Jumei Zhou ◽  
Fei Bai ◽  
Bonian Jiang ◽  
Juying Chen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Metastasis ◽  
Colon Cancer Metastasis ◽  
Endothelin A Receptor ◽  
Endothelin A

Specific endothelin-A-receptor antagonist ZD4054 inhibits breast cancer growth in vitro and in vivo

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
M Smollich ◽  
M Götte ◽  
J Fischgräbe ◽  
I Radke ◽  
L Macedo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Receptor Antagonist ◽  
Cancer Growth ◽  
Endothelin A Receptor ◽  
Endothelin A ◽  
Breast Cancer Growth

scholarly journals Cadherin-6B is proteolytically processed during epithelial-to-mesenchymal transitions of the cranial neural crest

2014 ◽  
Vol 25 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Andrew T. Schiffmacher ◽  
Rangarajan Padmanabhan ◽  
Sharon Jhingory ◽  
Lisa A. Taneyhill
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Spatiotemporal Pattern ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Crest Cell

The epithelial-to-mesenchymal transition (EMT) is a highly coordinated process underlying both development and disease. Premigratory neural crest cells undergo EMT, migrate away from the neural tube, and differentiate into diverse cell types during vertebrate embryogenesis. Adherens junction disassembly within premigratory neural crest cells is one component of EMT and, in chick cranial neural crest cells, involves cadherin-6B (Cad6B) down-regulation. Whereas Cad6B transcription is repressed by Snail2, the rapid loss of Cad6B protein during EMT is suggestive of posttranslational mechanisms that promote Cad6B turnover. For the first time in vivo, we demonstrate Cad6B proteolysis during neural crest cell EMT, which generates a Cad6B N-terminal fragment (NTF) and two C-terminal fragments (CTF1/2). Coexpression of relevant proteases with Cad6B in vitro shows that a disintegrin and metalloproteinases (ADAMs) ADAM10 and ADAM19, together with γ-secretase, cleave Cad6B to produce the NTF and CTFs previously observed in vivo. Of importance, both ADAMs and γ-secretase are expressed in the appropriate spatiotemporal pattern in vivo to proteolytically process Cad6B. Overexpression or depletion of either ADAM within premigratory neural crest cells prematurely reduces or maintains Cad6B, respectively. Collectively these results suggest a dual mechanism for Cad6B proteolysis involving two ADAMs, along with γ-secretase, during cranial neural crest cell EMT.

scholarly journals Role of endothelin-A receptor in cardiac neural crest cell fate

2011 ◽  
Vol 356 (1) ◽  
pp. 197-198
Author(s):  
Yanping Zhang ◽  
Mitchell T. McKnight ◽  
L. Bruno Ruest
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Crest Cell ◽  
Cardiac Neural Crest ◽  
Endothelin A Receptor ◽  
Endothelin A ◽  
Crest Cell

scholarly journals Endothelin A receptor is necessary for O2 constriction but not closure of ductus arteriosus

1999 ◽  
Vol 277 (4) ◽  
pp. H1521-H1531 ◽  
Author(s):  
F. Coceani ◽  
Y.-A. Liu ◽  
E. Seidlitz ◽  
L. Kelsey ◽  
T. Kuwaki ◽  
...  
Keyword(s):  
Genetically Modified ◽  
Ductus Arteriosus ◽  
Wild Type ◽  
Endothelin 1 ◽  
Dual Response ◽  
Endothelin A Receptor ◽  
Endothelin A ◽  
Constrictor Response

In vitro and in vivo techniques were developed with genetically modified mice to determine whether endothelin-1 (ET-1) functions as an O2 mediator in closure of the ductus arteriosus (DA) at birth. Wild-type CD-1 and 129/SvEv mice with ETA receptor −/−, +/−, and +/+ genotypes were used. Isolated DA from term ETA +/+ fetuses contracted to O2 (5–95%) and a thromboxane A2 analog (ONO-11113, 0.1 μM). Instead, ET-1 elicited a dual response with weak relaxation (0.1 nM) preceding contraction (1–100 nM). Indomethacin (2.8 μM) was also a constrictor. ETA−/− DA, unlike ETA +/+ DA, contracted marginally to O2and ET-1 but responded to ONO-11113. O2 contraction was also reduced in ETA +/− DA. In vivo, DA constricted equally in tracheotomized ETA −/− and ETA +/+ newborns. Conversely, no DA constriction was seen in hyperoxic ETA −/− fetuses in utero, although it occurred in ETA+/+ and +/− littermates. We conclude that ET-1 mediates the DA constrictor response to O2. Without ET-1, however, the vessel still closes postnatally, conceivably caused by the withdrawal of relaxing influence(s).

scholarly journals DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

2017 ◽  
Vol 216 (10) ◽  
pp. 3339-3354 ◽  
Author(s):  
Rebecca McLennan ◽  
Caleb M. Bailey ◽  
Linus J. Schumacher ◽  
Jessica M. Teddy ◽  
Jason A. Morrison ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Metastatic Melanoma ◽  
Neural Crest Cell ◽  
Bmp Signaling ◽  
Loss Of Function ◽  
Neural Crest Cell Migration ◽  
Crest Cell

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling.

Su2029 In Vivo Imaging of Mucosal Endothelin-a Receptor Expression to Characterize Murine Colorectal Cancer Development

2015 ◽  
Vol 148 (4) ◽  
pp. S-579
Author(s):  
Dominik Bettenworth ◽  
Marcus Mücke ◽  
Christiane Geyer ◽  
Carsten Höltke ◽  
Katrin Schwegmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
In Vivo Imaging ◽  
Receptor Expression ◽  
Cancer Development ◽  
Endothelin A Receptor ◽  
Endothelin A

Selective endothelin-a-receptor blockade reduces the growth of receptor-positive pancreatic cancer in vitro and in vivo

2003 ◽  
Vol 124 (4) ◽  
pp. A802
Author(s):  
Hubert G. Hotz ◽  
Birgit Hotz ◽  
Oscar J. Hines ◽  
Heinz J. Buhr ◽  
Howard A. Reber
Keyword(s):  
Pancreatic Cancer ◽  
Receptor Blockade ◽  
Endothelin A Receptor ◽  
Endothelin A
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