A retinoic acid receptor beta/gamma-selective prodrug (tazarotene) plus a retinoid X receptor ligand induces extracellular signal-regulated kinase activation, retinoblastoma hypophosphorylation, G0 arrest, and cell differentiation

Molecular Pharmacology
Andrew YenS Varvayanis

Abstract

Retinoic acid receptor (RAR)beta is perceived to function as a tumor suppressor gene in various contexts where its absence is associated with tumorigenicity and its presence causes cell cycle arrest. Tazarotene is a prodrug selective for RARbeta/gamma, thereby motivating interest in determining whether tazarotene might activate putative tumor suppressor activity. Using HL-60 human myeloblastic leukemia cells, a cell line that undergoes G0 cell cycle arrest and myeloid differentiation in response to retinoic acid (RA), tazarotene failed to cause extracellular signal-regulated kinase (ERK) activation, a requirement for retinoic acid (RA)-induced G0 arrest and differentiation; retinoblastoma (RB) hypophosphorylation, another characteristic of RA-induced G0 arrest and cell differentiation; G0 arrest; or differentiation into mature myeloid cells. However, when used in combination with a retinoid X receptor (RXR)-selective ligand, tazarotene caused ERK activation, RB tumor suppressor protein hypophosphorylation, G0 arrest, and myeloid differentiation. The kinetics of G0 arrest and differentiation was similar to that of RA. Dose-response studies showed that diminishing tazarotene progressively diminished both induced cell differentiat...Continue Reading

References

Feb 14, 1990·Biochemical and Biophysical Research Communications·Y HashimotoK Shudo
May 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M P GaubP Chambon
Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C NerviA M Jetten
Jan 13, 1995·The Journal of Biological Chemistry·S NagpalR A Chandraratna
Feb 25, 1996·Experimental Cell Research·S P SiM Peacocke
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·D DiSepioS Nagpal
Mar 13, 1999·International Journal of Cancer. Journal International Du Cancer·E WeberM Mabry
Nov 5, 1999·In Vitro Cellular & Developmental Biology. Animal·A YenS Varvayanis
Oct 31, 2001·Differentiation; Research in Biological Diversity·H Y HongA Yen

❮ Previous
Next ❯

Citations

Feb 9, 2010·Cellular and Molecular Life Sciences : CMLS·Maria TheodosiouMichael Schubert
Oct 26, 2005·Leukemia Research·Karel SoucekAlois Kozubík
Dec 17, 2017·Reproductive Sciences·Hanna HuebnerMatthias Ruebner

❮ Previous
Next ❯

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.