![]()
|
|
||||||||
J. Biol. Chem., Vol. 280, Issue 5, 3185-3196, February 4, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
from Sp1 Sites to Induce Cell Cycle Arrest in MCF-7 Breast Cancer Cell Line*

From the Cancer Research-UK Laboratories and Section of Cancer Cell Biology, Department of Cancer Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 ONN, United Kingdom
We used the estrogen-responsive MCF-7 breast cancer cell line as a relevant model to study the anti-proliferative effects of ICI182,780 and identified the negative cell cycle regulator p21Waf1 as a specific target of ICI182,780. Furthermore, silencing of the p21Waf1 expression by small interfering RNA overcame the G0/G1 cell cycle arrest induced by ICI182,780, suggesting that the induction of p21Waf1 expression has a direct role in mediating the ICI182,780-induced G0/G1 arrest. We further demonstrated that the induction of p21Waf1 by ICI182,780 is mediated at transcriptional and gene promoter levels through the proximal Sp1 sites located near the transcription start site. Co-immunoprecipitation, DNA "pull-down," and chromatin immunoprecipitation experiments together showed that in cycling cells, estrogen receptor
and histone deacetylase 1 (HDAC1) are recruited to the proximal Sp1 sites of the promoter to repress p21Waf1 expression. In the presence of ICI182,780, estrogen receptor
and HDACs are dissociated from Sp1, resulting in increased histone acetylation and de-repression of the p21Waf1 promoter and induction of p21Waf1 expression. The fact that p21Waf1 expression is normally repressed by HDAC activity in cycling cells is further demonstrated by the finding that p21Waf1 transcription can be induced by the silencing of HDACs with small interfering RNA or treatment with HDAC inhibitors.
Received for publication, July 16, 2004 , and in revised form, November 17, 2004.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 44-20-8383-5829; Fax: 44-20-8383-5830; E-mail: eric.lam{at}imperial.ac.uk.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
P. Jung, A. Menssen, D. Mayr, and H. Hermeking AP4 encodes a c-MYC-inducible repressor of p21 PNAS, September 30, 2008; 105(39): 15046 - 15051. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-C. Lin, J.-H. Lin, C.-W. Chou, Y.-F. Chang, S.-H. Yeh, and C.-C. Chen Statins Increase p21 through Inhibition of Histone Deacetylase Activity and Release of Promoter-Associated HDAC1/2 Cancer Res., April 1, 2008; 68(7): 2375 - 2383. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Bicaku, D. C. Marchion, M. L. Schmitt, and P. N. Munster Selective Inhibition of Histone Deacetylase 2 Silences Progesterone Receptor-Mediated Signaling Cancer Res., March 1, 2008; 68(5): 1513 - 1519. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Abukhdeir, M. I. Vitolo, P. Argani, A. M. De Marzo, B. Karakas, H. Konishi, J. P. Gustin, J. Lauring, J. P. Garay, C. Pendleton, et al. Tamoxifen-stimulated growth of breast cancer due to p21 loss PNAS, January 8, 2008; 105(1): 288 - 293. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. De los Santos, O. Martinez-Iglesias, and A. Aranda Anti-estrogenic actions of histone deacetylase inhibitors in MCF-7 breast cancer cells Endocr. Relat. Cancer, December 1, 2007; 14(4): 1021 - 1028. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Yu, X. Wang, C.-F. Ng, S. Chen, and F. L. Chan ERR{gamma} Suppresses Cell Proliferation and Tumor Growth of Androgen-Sensitive and Androgen-Insensitive Prostate Cancer Cells and Its Implication as a Therapeutic Target for Prostate Cancer Cancer Res., May 15, 2007; 67(10): 4904 - 4914. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hiscox, N. J Jordan, W. Jiang, M. Harper, R. McClelland, C. Smith, and R. I Nicholson Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast cancer cells: implications for tumour-stroma interactions Endocr. Relat. Cancer, December 1, 2006; 13(4): 1085 - 1099. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Jaber, T. Gao, L. Huang, S. Karmakar, and C. L. Smith The Pure Estrogen Receptor Antagonist ICI 182,780 Promotes a Novel Interaction of Estrogen Receptor-{alpha} with the 3',5'-Cyclic Adenosine Monophosphate Response Element-Binding Protein-Binding Protein/p300 Coactivators Mol. Endocrinol., November 1, 2006; 20(11): 2695 - 2710. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Stossi, V. S. Likhite, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Estrogen-occupied Estrogen Receptor Represses Cyclin G2 Gene Expression and Recruits a Repressor Complex at the Cyclin G2 Promoter J. Biol. Chem., June 16, 2006; 281(24): 16272 - 16278. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Castet, A. Herledan, S. Bonnet, S. Jalaguier, J.-M. Vanacker, and V. Cavailles Receptor-Interacting Protein 140 Differentially Regulates Estrogen Receptor-Related Receptor Transactivation Depending on Target Genes Mol. Endocrinol., May 1, 2006; 20(5): 1035 - 1047. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-J. Hung, Y.-T. Wang, and W.-C. Chang Sp1 Deacetylation Induced by Phorbol Ester Recruits p300 To Activate 12(S)-Lipoxygenase Gene Transcription. Mol. Cell. Biol., March 1, 2006; 26(5): 1770 - 1785. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Liu, N. Pore, M. Kim, K. R. Voong, M. Dowling, A. Maity, and G. D. Kao Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription Factors Mol. Biol. Cell, February 1, 2006; 17(2): 585 - 597. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |