Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Campbell, P. M.
Right arrow Articles by Szyf, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Campbell, P. M.
Right arrow Articles by Szyf, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol. 24, No. 1, 17-24, January 2003
© 2003 Oxford University Press

CANCER BIOLOGY

Human DNA methyltransferase gene DNMT1 is regulated by the APC pathway

Paul M. Campbell and Moshe Szyf1

Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1Y6

Epigenomic changes in DNA methylation patterns are evident in a variety of cancers, including colorectal cancer (CRC). In addition, a large proportion of CRC tumors and cell lines harbor genetic mutations in the APC/ß-catenin/TCF transcription activation pathway. While several target genes have been proposed, a causal downstream agent between APC mutation and cancer has not been fully established. Because previous work implicates DNA methyltransferase (DMNT1) as a critical point in tumorigenesis and recent studies suggest that familial CRC also exhibits epigenetic alterations, we sought to investigate whether this gene might be regulated by APC in CRC. Reconstitution of wild type APC in HT-29 CRC cell lines reduced the expression of both a reporter gene driven by the minimal DNMT1 promoter and DNMT1 mRNA that is independent of cell growth stasis. We also provide evidence for a causal role of DNMT1 in CRC by demonstrating that antisense-driven reduction of DNMT1 mRNA inhibits anchorage-independent growth, an indicator of tumorigenesis, of CRC cells. These data support future consideration of DNMT1 as a target in the treatment of CRC.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
N. Shivapurkar, V. Stastny, N. Okumura, L. Girard, Y. Xie, C. Prinsen, F. B. Thunnissen, I. I. Wistuba, B. Czerniak, E. Frenkel, et al.
Cytoglobin, the Newest Member of the Globin Family, Functions as a Tumor Suppressor Gene
Cancer Res., September 15, 2008; 68(18): 7448 - 7456.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Shevchuk, L. Kretzner, K. Munson, J. Axume, J. Clark, O. V. Dyachenko, M. Caudill, Y. Buryanov, and S. S. Smith
Transgene-induced CCWGG methylation does not alter CG methylation patterning in human kidney cells
Nucleic Acids Res., October 24, 2005; 33(19): 6124 - 6136.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Ghoshal, J. Datta, S. Majumder, S. Bai, H. Kutay, T. Motiwala, and S. T. Jacob
5-Aza-Deoxycytidine Induces Selective Degradation of DNA Methyltransferase 1 by a Proteasomal Pathway That Requires the KEN Box, Bromo-Adjacent Homology Domain, and Nuclear Localization Signal
Mol. Cell. Biol., June 1, 2005; 25(11): 4727 - 4741.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.