CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Farias, E. F.
Right arrow Articles by Mira-y-Lopez, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farias, E. F.
Right arrow Articles by Mira-y-Lopez, R.
Cell Growth & Differentiation Vol. 13, 335-341, August 2002
© 2002 American Association for Cancer Research

Retinoic Acid Receptor {alpha}2 Is a Growth Suppressor Epigenetically Silenced In MCF-7 Human Breast Cancer Cells1

Eduardo F. Farias, Alice Arapshian, Ira J. Bleiweiss, Samuel Waxman, Arthur Zelent and Rafael Mira-y-Lopez2

Departments of Medicine [E. F. F., A. A., S. W., R. M. L.] and Pathology (I. J. B.), Mount Sinai School of Medicine, New York, New York 10029-6574, and Leukaemia Research Fund Centre, Institute of Cancer Research, London SW3 6JB, United Kingdom [A. Z.]

Retinoic acid (RA) receptor (RAR) ß2 has been shown to be underexpressed in human breast cancer cells, including MCF-7 cells, and recent reports have suggested that hypermethylation of the RARß2 promoter and 5'-UTR is the underlying cause. Here we show that RAR{alpha}2 is also underexpressed in MCF-7 breast cancer cells, at both the message and the protein level, relative to normal or nontumorigenic breast epithelial cells. Bisulfite sequencing of the CpG island in the RAR{alpha}2 promoter revealed highly penetrant and uniform cytosine methylation in MCF-7 cells. Pretreatment with the DNA methyltransferase inhibitor, azacytidine, followed by treatment with RA and a histone deacetylase inhibitor, trichostatin A, resulted in partial promoter demethylation and RAR{alpha}2 induction, which strongly suggested that promoter hypermethylation is responsible for RAR{alpha}2 underexpression. We compared the outcome of ectopic expression in MCF-7 cells of matched levels of RAR{alpha}2 and RARß2. On the basis of a clonogenic assay, RAR{alpha}2 displayed ligand-dependent growth-suppressive activity similar to that of RARß2; thus, 10 and 20 nM RA inhibited clonogenic growth by 52 and 80%, respectively, in RAR{alpha}2-transfected cells compared with 75 and 77%, respectively, in RARß2-transfected cells. We conclude that the silencing of the RAR{alpha}2 promoter by hypermethylation may play a contributory role in the dysregulation of RA signaling in mammary tumorigenesis.




This article has been cited by other articles:


Home page
Cancer Res.Home page
J. Srivastava, C. L. Robertson, D. Rajasekaran, R. Gredler, A. Siddiq, L. Emdad, N. D. Mukhopadhyay, S. Ghosh, P. B. Hylemon, G. Gil, et al.
AEG-1 Regulates Retinoid X Receptor and Inhibits Retinoid Signaling
Cancer Res., August 15, 2014; 74(16): 4364 - 4377.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
N. P. Mongan and L. J. Gudas
Valproic acid, in combination with all-trans retinoic acid and 5-aza-2'-deoxycytidine, restores expression of silenced RAR{beta}2 in breast cancer cells
Mol. Cancer Ther., March 1, 2005; 4(3): 477 - 486.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
B. Bourachot, M. Yaniv, and C. Muchardt
Growth inhibition by the mammalian SWI-SNF subunit Brm is regulated by acetylation
EMBO J., December 15, 2003; 22(24): 6505 - 6515.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
K. Gumireddy, L. N. Sutton, P. C. Phillips, and C. D. Reddy
All-trans-Retinoic Acid-induced Apoptosis in Human Medulloblastoma: Activation of Caspase-3/Poly(ADP-ribose) Polymerase 1 Pathway
Clin. Cancer Res., September 15, 2003; 9(11): 4052 - 4059.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2002 by the American Association of Cancer Research.