A Retinoic Acid Receptor β/γ-Selective Prodrug (tazarotene) Plus a Retinoid X Receptor Ligand Induces Extracellular Signal-Regulated Kinase Activation, Retinoblastoma Hypophosphorylation, G0Arrest, and Cell Differentiation

2004 ◽  
Vol 66 (6) ◽  
pp. 1727-1737 ◽  
Author(s):  
Andrew Yen ◽  
Robert Fenning ◽  
Roshantha Chandraratna ◽  
Patricia Walker ◽  
Susi Varvayanis
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Receptor Ligand ◽  
Kinase Activation ◽  
Acid Receptor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

scholarly journals Antagonistic Interactions between Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase and Retinoic Acid Receptor Signaling in Colorectal Cancer Cells

2017 ◽  
Vol 37 (15) ◽  
Author(s):  
Masamichi Imajo ◽  
Kunio Kondoh ◽  
Takuya Yamamoto ◽  
Kei Nakayama ◽  
May Nakajima-Koyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Retinoic Acid ◽  
Map Kinases ◽  
Retinoic Acid Receptor ◽  
Cell Fates ◽  
Acid Receptor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Antagonistic Interactions

ABSTRACT Deregulated activation of RAS/extracellular signal-regulated kinase (ERK) signaling and defects in retinoic acid receptor (RAR) signaling are both implicated in many types of cancers. However, interrelationships between these alterations in regulating cancer cell fates have not been fully elucidated. Here, we show that RAS/ERK and RAR signaling pathways antagonistically interact with each other to regulate colorectal cancer (CRC) cell fates. We show that RAR signaling activation promotes spontaneous differentiation of CRC cells, while ERK activation suppresses it. Our microarray analyses identify genes whose expression levels are upregulated by RAR signaling. Notably, one of these genes, MKP4, encoding a member of dual-specificity phosphatases for mitogen-activated protein (MAP) kinases, mediates ERK inactivation upon RAR activation, thereby promoting the differentiation of CRC cells. Moreover, our results also show that RA induction of RAR target genes is suppressed by the ERK pathway activation. This suppression results from the inhibition of RAR transcriptional activity, which is shown to be mediated through an RIP140/histone deacetylase (HDAC)-mediated mechanism. These results identify antagonistic interactions between RAS/ERK and RAR signaling in the cell fate decision of CRC cells and define their underlying molecular mechanisms.

Ligand-inducible retinoid X receptor-mediated protein: DNA interactions in the retinoic acid receptor β2 gene promoter in vivo

1998 ◽  
Vol 136 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Masato Ikeda ◽  
Remco A Spanjaard ◽  
Elizabeth W Noordhoek ◽  
Akio Kawaguchi ◽  
Toshimasa Onaya ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Gene Promoter ◽  
Retinoid X Receptor ◽  
Dna Interactions ◽  
Acid Receptor ◽  
Protein Dna Interactions ◽  
Retinoic Acid Receptor Β2

scholarly journals Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2

2019 ◽  
Vol 20 (9) ◽  
pp. 2071 ◽  
Author(s):  
Mengying Yu ◽  
Lei Zhang ◽  
Yingxiang Liu ◽  
Defu Liu ◽  
Zekun Guo
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Embryonic Carcinoma ◽  
Extracellular Signal ◽  
Embryonic Carcinoma Cells ◽  
Embryonic Carcinoma Cell ◽  
Mediate Cell

Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets α/β-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.

scholarly journals Retinoic acid receptor α and retinoid-X receptor-specific agonists synergistically target telomerase expression and induce tumor cell death

Oncogene ◽  
2003 ◽  
Vol 22 (57) ◽  
pp. 9142-9150 ◽  
Author(s):  
Frédéric Pendino ◽  
Charles Dudognon ◽  
Francois Delhommeau ◽  
Tewfik Sahraoui ◽  
Maria Flexor ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Tumor Cell ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Tumor Cell Death ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

The Combination of 9-cis Retinoic Acid Plus MEK Inhibitor Induces Apoptosis Via Dephosphorylation of Retinoid X Receptor α in HL-60R Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1927-1927
Author(s):  
Nobuhiro Kanemura ◽  
Hisashi Tsurumi ◽  
Senji Kasahara ◽  
Takeshi Hara ◽  
Toshiki Yamada ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Retinoic Acid Receptor ◽  
Biological Activities ◽  
Combined Treatment ◽  
Mek Inhibitor ◽  
Retinoid X Receptor ◽  
Dominant Negative ◽  
Expression Level ◽  
Hcc Cells

Abstract Resistance against retinoic acid (RA) is a serious problem of differentiation-induction therapy for acute promyelocytic leukemia (APL) in clinical practice. RA exerts its biological activities primarily through the nuclear receptor dimmer, consisting of retinoic acid receptor (RAR) and retinoid X receptor (RXR). Both receptors consist of three subtypes (α, β and γ) and form heterodimeric RAR/RXR and homodimeric RXR/RXR complexes. 9-cis RA, which is a high-affinity ligand for RXR but also binds to RAR, induces cell differentiation in wild type HL-60 human myeloid leukemia cells. However, in HL-60R cells, the RA-resistant subclone of HL-60, 9-cis RA can not induce cell differentiation and apoptosis. We recently reported that malfunction of RXRα due to posttranslational modification by phosphorylation to be associated with carcinogenesis of hepatocellular carcinoma (HCC). Phosphorylated form of RXRα (p-RXRα) at serine 260 by Ras/MAPK is resistant to ubiquitin/proteasome-mediated degradation and the accumulation of p-RXRα interferes with the function of remaining normal RXRα in a dominant negative manner, thereby promoting growth of HCC cells. We also found that in the presence of MEK inhibitor PD98059, 9-cis RA can induce the degradation of p-RXRα and thus restoring the function of this receptor in RXRα-phosphorylated human HCC cells. Based on the results as described above, we initiated this study to examine whether 9-cis RA can exert growth inhibitory effects on RA-resistant HL-60R cells when combined with MEK inhibitor, with focusing on the inhibition of expression of p-RXRα protein. We found that RXRα protein was originally expressed in both HL-60 and HL-60R cells, and that the expression level of RXRα protein was inhibited by about 60% and 20%, respectively, when those cells were treated with 0.5 μM 9-cis RA. Not only total RXRα protein, but also the level of p-RXRα protein was constitutively expressed in both HL-60 and HL-60R cells, and was significantly decreased in HL-60 cells by treatment with 9-cis RA alone. On the other hand, in HL-60R cells, 9-cis RA alone nor 20 μM PD98059 alone did not cause a down regulation of these proteins. However, when HL-60R cells were treated with the combination of 9-cis RA plus PD98059, the expression level of p-RXRα protein was markedly decreased. Moreover, the combination of these agents induced apoptosis in HL-60R cells, whereas similar effect was not obtained when the cells were treated with either agent alone. The combined treatment of these agents also cooperatively inhibited the growth of HL-60 R cells. The present findings suggest that the accumulation of p-RXRα might impair the function of normal RXRα as a master regulator of nuclear receptors and, thus, contributing to the resistance to RA in HL-60R cells. Combination of 9-cis RA plus MEK inhibitor might be an effective regimen for patients with RA resistant APL.

ChemInform Abstract: Synthesis and Characterization of a Highly Potent and Selective Isotopically Labeled Retinoic Acid Receptor Ligand, ALRT1550.

ChemInform ◽  
2010 ◽  
Vol 29 (27) ◽  
pp. no-no
Author(s):  
Y. L. BENNANI ◽  
K. S. MARRON ◽  
D. E. MAIS ◽  
K. FLATTEN ◽  
A. M. NADZAN ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Synthesis And Characterization ◽  
Receptor Ligand ◽  
Acid Receptor
Sign in / Sign up

Export Citation Format

Share Document