help button home button Endocrine Society Molecular Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on April 13, 2006
Molecular Endocrinology, doi:10.1210/me.2005-0321
A more recent version of this article appeared on September 1, 2006
This Article
Right arrow Author Manuscript (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
20/9/2109    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow NURSA Molecule Pages Link
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lefebvre, B.
Right arrow Articles by Lefebvre, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lefebvre, B.
Right arrow Articles by Lefebvre, P.

Submitted on August 4, 2005
Accepted on April 3, 2006

Down-regulation of the tumor suppressor gene RAR{beta}2 through the PI3K/Akt signaling pathway

Bruno Lefebvre*, Céline Brand, Sébastien Flajollet, and Philippe Lefebvre

INSERM U459, Faculté de Médecine Henri Warembourg, 1 Place de Verdun, 59045 Lille cedex, France

* To whom correspondence should be addressed. E-mail: bruno.lefebvre{at}lille.inserm.fr.

The retinoic acid receptor (RAR) beta 2 (RAR{beta}2) is a potent, retinoid-inducible tumor suppressor gene, which is a critical molecular relay for retinoid actions in cells. Its down-regulation, or loss of expression, leads to resistance of cancer cells to retinoid treatment. Up to now, no primary mechanism underlying the repression of the RAR{beta}2 gene expression, hence affecting cellular retinoid sensitivity, has been identified. Here we demonstrate that the PI3K/Akt signaling pathway affects cellular retinoid sensitivity, by regulating corepressor recruitment to the RAR{beta}2 promoter. Through direct phosphorylation of the corepressor SMRT, Akt stabilized RAR/SMRT interaction, leading to an increased tethering of SMRT to the RAR{beta}2 promoter, decreased histone acetylation, down-regulation of the RAR{beta}2 expression and impaired cellular differentiation in response to retinoid. The PI3K/Akt signaling pathway, an important modulator of cellular survival, has thus a direct impact on cellular retinoid sensitivity and its deregulation may be the trigerring event in retinoid resistance of cancer cells.
Key words: corepressor • histone acetylation • retinoic acid • retinoic acid receptor beta2 • tumor suppressor

NURSA Molecule Pages Link:

Nuclear Receptors:   RARβ
Coregulators:   NCOR  |  SMRT
Ligands:   all-trans-Retinoic acid



This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
M. De los Santos, A. Zambrano, A. Sanchez-Pacheco, and A. Aranda
Histone Deacetylase Inhibitors Regulate Retinoic Acid Receptor {beta} Expression in Neuroblastoma Cells by Both Transcriptional and Posttranscriptional Mechanisms
Mol. Endocrinol., October 1, 2007; 21(10): 2416 - 2426.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
M. V. Karamouzis, P. A. Konstantinopoulos, and A. G. Papavassiliou
The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis
Mol. Cancer Res., February 1, 2007; 5(2): 109 - 120.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
C. W. Xiao, J. Mei, W. Huang, C. Wood, M. R. L'Abbe, G. S. Gilani, G. M. Cooke, and I. H. Curran
Dietary Soy Protein Isolate Modifies Hepatic Retinoic Acid Receptor-{beta} Proteins and Inhibits Their DNA Binding Activity in Rats
J. Nutr., January 1, 2007; 137(1): 1 - 6.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2006 by The Endocrine Society