Skip Navigation



Carcinogenesis Advance Access published online on May 11, 2005
Carcinogenesis, doi:10.1093/carcin/bgi120
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/9/1503    most recent
bgi120v1
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Dihlmann, S.
Right arrow Articles by von Knebel Doeberitz, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dihlmann, S.
Right arrow Articles by von Knebel Doeberitz, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received January 13, 2005
Revised April 7, 2005
Accepted May 3, 2005

CANCER BIOLOGY

Regulation of AKT1 expression by beta-catenin/Tcf/Lef signaling in colorectal cancer cells

Susanne Dihlmann 1*, Matthias Kloor 1, Christine Fallsehr 1, and Magnus von Knebel Doeberitz 1

1 Institute of Molecular Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany

* To whom correspondence should be addressed.
Susanne Dihlmann, E-mail: susanne.dihlmann{at}med.uni-heidelberg.de


  Abstract

The serin/threonine kinase AKT plays a critical role in controlling the balance between cell survival and apoptosis. Several reports implicated AKT in the molecular pathogenesis of different human malignancies and overexpression of AKT was recently demonstrated to be an early event in colorectal carcinogenesis. We here report the identification of nine putative Tcf/Lef-binding elements (TBEs) upstream to the ATG initiation site of the AKT1 gene. Four of these TBEs are located upstream of the transcriptional start whereas five TBEs are situated in Exon 1 of the AKT1 gene. Accordingly, we hypothesized that AKT1 expression might be regulated by Wnt/{beta}-catenin signaling. To elucidate the regulation of AKT expression in colon cancer cells we generated reporter constructs containing the luciferase gene under control of different regions derived from the AKT1 promoter/enhancer. Transient expression of the constructs in colorectal cancer cell lines resulted in significant activation of the reporter gene. Luciferase was stimulated 20- to 50-fold in SW480, SW948, and HCT116 colorectal cancer cells. In contrast, the AKT1 promoter/enhancer constructs showed only a weak response in 293 embryonic kidney cells. Coexpression of a constitutively active {beta}-catenin mutant in colon cancer cells further enhanced reporter gene activation from the AKT1 promoter/enhancer, whereas it was downregulated by introduction of either wild-type APC or dnTcf-4. In addition, immunohistochemical staining of tumor sections derived from colorectal cancer patients showed elevated expression levels of AKT1, correlating with enhanced cytoplasmic/nuclear expression of {beta}-catenin. In summary our data suggest that {beta}-catenin/Tcf contributes to the transcriptional regulation of the AKT1 gene.

Keywords: Wnt; {beta}-catenin; colon; AKT; promoter; enhancer; signal transduction.
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
 J. Biol. Chem.Home page
K. N. Nejak-Bowen, G. Zeng, X. Tan, B. Cieply, and S. P. Monga
{beta}-Catenin Regulates Vitamin C Biosynthesis and Cell Survival in Murine Liver
J. Biol. Chem., October 9, 2009; 284(41): 28115 - 28127.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
Z. Wang, A. Havasi, J. M. Gall, H. Mao, J. H. Schwartz, and S. C. Borkan
{beta}-Catenin Promotes Survival of Renal Epithelial Cells by Inhibiting Bax
J. Am. Soc. Nephrol., September 1, 2009; 20(9): 1919 - 1928.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Senthivinayagam, P. Mishra, S. K. Paramasivam, S. Yallapragada, M. Chatterjee, L. Wong, A. Rana, and B. Rana
Caspase-mediated Cleavage of {beta}-Catenin Precedes Drug-induced Apoptosis in Resistant Cancer Cells
J. Biol. Chem., May 15, 2009; 284(20): 13577 - 13588.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Martinez-Cardus, E. Martinez-Balibrea, E. Bandres, R. Malumbres, A. Gines, J. L. Manzano, M. Taron, J. Garcia-Foncillas, and A. Abad
Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer
Mol. Cancer Ther., January 1, 2009; 8(1): 194 - 202.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
L. A. Scheving, M. C. Stevenson, X. Zhang, and W. E. Russell
Cultured rat hepatocytes upregulate Akt and ERK in an ErbB-2-dependent manner
Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G322 - G331.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. A. Crowell, V. E. Steele, and J. R. Fay
Targeting the AKT protein kinase for cancer chemoprevention
Mol. Cancer Ther., August 1, 2007; 6(8): 2139 - 2148.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Z. Cheng, J. Chan, Q. Wang, W. Zhang, C. D. Sun, and L.-H. Wang
Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel
Cancer Res., March 1, 2007; 67(5): 1979 - 1987.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
R. Hu, T. O. Khor, G. Shen, W.-S. Jeong, V. Hebbar, C. Chen, C. Xu, B. Reddy, K. Chada, and A.-N. T. Kong
Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable
Carcinogenesis, October 1, 2006; 27(10): 2038 - 2046.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. M. L. Coluccia, D. Benati, H. Dekhil, A. De Filippo, C. Lan, and C. Gambacorti-Passerini
SKI-606 Decreases Growth and Motility of Colorectal Cancer Cells by Preventing pp60(c-Src)-Dependent Tyrosine Phosphorylation of {beta}-Catenin and Its Nuclear Signaling
Cancer Res., February 15, 2006; 66(4): 2279 - 2286.
[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.