Retinoic acid receptor isoform RAR? 1: an antagonist of the transactivation of the RAR? RARE in epithelial cell lines and normal human keratinocytes

1993 ◽  
Vol 17 (1) ◽  
pp. 35-45 ◽  
Author(s):  
C. Miquel ◽  
C. Clusel ◽  
A. Semat ◽  
C. Gerst ◽  
M. Darmon
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Retinoic Acid Receptor ◽  
Human Keratinocytes ◽  
Acid Receptor ◽  
Normal Human Keratinocytes ◽  
Epithelial Cell Lines ◽  
Normal Human

Effects of Retinoic Acid on lnterleukin-1α and -1β Expression by Normal Human Keratinocytes Cultured in Defined Medium

1993 ◽  
Vol 6 (1) ◽  
pp. 10-19 ◽  
Author(s):  
Hugues Gatto ◽  
Marie-Hélène Richard ◽  
Jacqueline Viac ◽  
Marie Charveron ◽  
Daniel Schmitt
Keyword(s):  
Retinoic Acid ◽  
Human Keratinocytes ◽  
Defined Medium ◽  
Normal Human Keratinocytes ◽  
Normal Human

Expression of retinoic acid receptor alpha mRNA in human leukemia cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 99-102 ◽  
Author(s):  
C Largman ◽  
K Detmer ◽  
JC Corral ◽  
FM Hack ◽  
HJ Lawrence
Keyword(s):  
Retinoic Acid ◽  
Cell Lines ◽  
Retinoic Acid Receptor ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Retinoic Acid Receptor Alpha ◽  
Acid Receptor ◽  
Receptor Alpha ◽  
Human Leukemia Cells

The expression of the newly described human retinoic acid receptor alpha (RAR alpha) in six nonlymphoid and six lymphoid leukemia cell lines and nine freshly obtained samples of leukemia cells from patients with acute nonlymphoid leukemia was assessed by Northern blot analysis, using a full length cDNA clone of RAR alpha as probe. RAR alpha was expressed in all 12 cell lines and in all fresh leukemia samples as two major transcripts of 2.6 and 3.5 kb in size. Levels of RAR alpha expression and transcript sizes in retinoid-sensitive cells (such as HL60 or fresh promyelocytic leukemia cells) were not different from those in other samples. Moreover, expression of RAR alpha was not significantly modulated by exposure to cis-retinoic acid (cisRA) in either cisRA-responsive or unresponsive cells. By using a 3′ fragment of the RAR alpha gene as a probe, we confirmed that the transcripts visualized did not represent the homologous RAR beta gene. RAR alpha appears to be expressed in most human leukemia cells regardless of the type of biologic response to retinoic acid.

Pharicin B, a Novel Diterpenoid, Stabilizes Retinoic Acid Receptor-α Protein and Induces Differentiation of AML Cells in the Presence of Physiological Doses of ATRA.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1601-1601
Author(s):  
Guo-Qiang Chen ◽  
Zhi-Min Gu ◽  
Mei-Yi Zhou ◽  
Ying-Li Wu ◽  
Ying Huang
Keyword(s):  
Retinoic Acid ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Retinoic Acid Receptor ◽  
Chinese Herb ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Dietary Vitamin ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α

Abstract Retinoids, a generic term that covers compounds including both naturally dietary vitamin A (retinol) metabolites and active synthetic analogs, exert their pleiotropic effects such as anticancer activity through the three retinoic acid receptors (RARs) subtypes [RARα, RARβ and RARγ]. The most impressive example of retinoid anticancer activity is the successful application of all-trans retinoic acid (ATRA) in the treatment of patients with acute promyelocytic leukemia (APL), a unique subtype of acute myelogenous leukemia (AML) which characterized with the specific reciprocal chromosome translocation t(15;17) that results in the expression of leukemia-promoting promyelocytic leukemia-retinoic acid receptor-α (PML-RARα) chimeric protein. However, retinoid resistance frequently occurred in ATRA-treated patients. Isodon xerophilus, a perennial shrub native to Southern China, has been used as an anti-tumor, anti-inflammatory, and anti-microbial agent in Chinese herb medicine for a long history. During the past 30 years, a large number of ent-kauranoids have been isolated from the genus Isodon, many of which exhibit potent antitumor activities with a relatively low toxicity. In this work, we identified a novel ent-kaurene diterpenoid named pharicin B to rapidly stabilize RARα as well as PML-RARα protein in AML cell lines. More intriguingly, it also antagonizes ATRA-induced degradation of RARα and PML-RARα proteins. The interesting finding promotes us to investigate its possible effects on AML cells. Our results demonstrated that pharicin B at nontoxic concentration suppresses growth in APL cell line NB4 and myeloblactic leukemic U937 and THP-1 cell lines. Together with exceedingly low concentration of ATRA and RARα specific agonist AM580 existed, pharicin B significantly triggered all the three cell lines and some NB4-derived ATRA-resistant cell lines such as NB4-MR2 and NB4-LR1 (but not NB4-LR2) to undergo myeloid maturation, as evidenced by morphology, CD11/CD14 expression and NBT reduction test. All these results proposed that pharicin B would be a good tool for investigating mechanisms of RARα stabilization and degradation induced by ATRA as well as retinoid resistance, and its combination with ATRA might present the clinical potentials for differentiation-inducing therapy of APL and other AML patients.

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