© 2004 by Oxford University Press
© 2004 Oxford University Press
ARTICLE |
Associations Among 
-TrCP, an E3 Ubiquitin Ligase Receptor, -Catenin, and NF-
B in Colorectal Cancer
Affiliations of authors: Divisions of Diagnostic Molecular Oncology (AO, BZ, TM) and Surgical Oncology (KY, MM, TM), Cancer Research Institute, Kanazawa University, Kanazawa, Japan; Molecular Laboratory, Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan (VB); Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia (SYF)
Correspondence to: Toshinari Minamoto, MD, PhD, Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan (e-mail: minamot{at}kenroku.kanazawa-u.ac.jp)
Background: The ubiquitin–proteasome pathway is important in regulating protein signaling pathways that are involved in tumorigenesis. 
-transducin repeat–containing proteins (-TrCP) are components of the ubiquitin ligase complex targeting -catenin and I
B
for proteasomal degradation and are thus a negative regulator of Wnt/-catenin signaling and a positive regulator of NF-B signaling. We analyzed expression of -TrCP in colorectal cancers and its association with types of -catenin subcellular localization, an indirect measure of activation. Methods: Levels of -TrCP1 mRNA and protein were measured by quantitative reverse transcription–polymerase chain reaction and immunoblotting, respectively, in samples of tumor and normal tissues from 45 patients with colorectal cancer. Types of -catenin activation (diffuse or invasion edge) and NF-B activation were examined by immunohistochemistry. Apoptosis was determined by the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick-end labeling (TUNEL) assay. All statistical tests were two-sided. Results: Compared with the -TrCP1 levels in normal tissues, 25 (56%) of 45 tumors had increased -TrCP1 mRNA and protein levels. Of the 22 (49%) tumors with -catenin activation, 12 had the diffuse type (i.e., nuclear accumulation throughout the tumor) and 10 had the invasion edge type (i.e., nuclear accumulation predominantly in the tumor cells that formed the invasion edge). Increased -TrCP1 levels were statistically significantly associated with -catenin activation (P = .023) and decreased apoptosis (P = .035). -TrCP accumulated in the nuclei of tumor cells that contained increased levels of -TrCP1 mRNA and the active form of NF-B. Higher levels of -TrCP1 mRNA were detected in primary tumors of patients who had metastases (0.960 arbitrary units, 95% confidence interval = 0.878 to 1.042) than in the tumors of patients who did not (0.722 arbitrary units, 95% confidence interval = 0.600 to 0.844; P = .016). Conclusion: In colorectal cancer, increased expression of -TrCP1 is associated with activation of both -catenin and NF-B, suggesting that the integration of these signaling pathways by increased -TrCP expression may contribute to an inhibition of apoptosis and tumor metastasis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. A. Kimbrel and A. L. Kung The F-box Protein {beta}-TrCp1/Fbw1a Interacts with p300 to Enhance {beta}-Catenin Transcriptional Activity J. Biol. Chem., May 8, 2009; 284(19): 13033 - 13044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, P. A. Wood, C. M. Ansell, M. Ohmori, E.-Y. Oh, Y. Xiong, F. G. Berger, M. M. O. Pena, and W. J.M. Hrushesky {beta}-Catenin Induces {beta}-TrCP-Mediated PER2 Degradation Altering Circadian Clock Gene Expression in Intestinal Mucosa of ApcMin/+ Mice J. Biochem., March 1, 2009; 145(3): 289 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Ougolkov, V. N. Bilim, and D. D. Billadeau Regulation of Pancreatic Tumor Cell Proliferation and Chemoresistance by the Histone Methyltransferase Enhancer of Zeste Homologue 2 Clin. Cancer Res., November 1, 2008; 14(21): 6790 - 6796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Gu, G. T. Bowden, D. Normolle, and Y. Sun SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and I{kappa}B-{alpha}/NF-{kappa}B J. Cell Biol., September 7, 2007; 178(6): 1009 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Nolz, M. E. Fernandez-Zapico, and D. D. Billadeau TCR/CD28-Stimulated Actin Dynamics Are Required for NFAT1-Mediated Transcription of c-rel Leading to CD28 Response Element Activation J. Immunol., July 15, 2007; 179(2): 1104 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Lehman, R. Tibshirani, J. Y. Hsu, Y. Natkunam, B. T. Harris, R. B. West, M. A. Masek, K. Montgomery, M. van de Rijn, and P. K. Jackson Oncogenic Regulators and Substrates of the Anaphase Promoting Complex/Cyclosome Are Frequently Overexpressed in Malignant Tumors Am. J. Pathol., May 1, 2007; 170(5): 1793 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Winteringham, R. Endersby, S. Kobelke, R. K. McCulloch, J. H. Williams, J. Stillitano, S. M. Cornwall, E. Ingley, and S. P. Klinken Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule J. Biol. Chem., December 15, 2006; 281(50): 38791 - 38800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Ougolkov, M. E. Fernandez-Zapico, V. N. Bilim, T. C. Smyrk, S. T. Chari, and D. D. Billadeau Aberrant Nuclear Accumulation of Glycogen Synthase Kinase-3{beta} in Human Pancreatic Cancer: Association with Kinase Activity and Tumor Dedifferentiation Clin. Cancer Res., September 1, 2006; 12(17): 5074 - 5081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yasumoto, K. Koizumi, A. Kawashima, Y. Saitoh, Y. Arita, K. Shinohara, T. Minami, T. Nakayama, H. Sakurai, Y. Takahashi, et al. Role of the CXCL12/CXCR4 Axis in Peritoneal Carcinomatosis of Gastric Cancer Cancer Res., February 15, 2006; 66(4): 2181 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-T. Lin, C.-Y. Zuon, C.-C. Chang, S.-T. Chen, C.-P. Chen, B.-R. Lin, M.-Y. Wang, Y.-M. Jeng, K.-J. Chang, P.-H. Lee, et al. Cyr61 Induces Gastric Cancer Cell Motility/Invasion via Activation of the Integrin/Nuclear Factor-{kappa}B/Cyclooxygenase-2 Signaling Pathway Clin. Cancer Res., August 15, 2005; 11(16): 5809 - 5820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koch, A. Waha, W. Hartmann, A. Hrychyk, U. Schuller, A. Waha, K. A. Wharton Jr, S. Y. Fuchs, D. v. Schweinitz, and T. Pietsch Elevated Expression of Wnt Antagonists Is a Common Event in Hepatoblastomas Clin. Cancer Res., June 15, 2005; 11(12): 4295 - 4304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Muerkoster, A. Arlt, B. Sipos, M. Witt, M. Grossmann, G. Kloppel, H. Kalthoff, U. R. Folsch, and H. Schafer Increased Expression of the E3-Ubiquitin Ligase Receptor Subunit {beta}TRCP1 Relates to Constitutive Nuclear Factor-{kappa}B Activation and Chemoresistance in Pancreatic Carcinoma Cells Cancer Res., February 15, 2005; 65(4): 1316 - 1324. [Abstract] [Full Text] [PDF]
|
|