This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mei, J. M. Articles by Phang, J. M. Search for Related Content PubMed PubMed Citation Articles by Mei, J. M. Articles by Phang, J. M.

Differential Formation of ß-Catenin/Lymphoid Enhancer Factor-1 DNA Binding Complex Induced by Nitric Oxide in Mouse Colonic Epithelial Cells Differing in Adenomatous Polyposis Coli (Apc) Genotype

Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute [J. M. M., N. G. H., S. P. D., J. M. P], and Intramural Research Support Program, Science Applications International Corporation-Frederick [D. F. W.], National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702

Increased cytoplasmic ß-catenin levels and the associated nuclear ß-catenin/T-cell factor (Tcf)-lymphoid enhancer factor (LEF) complex formation have been frequently found in colon cancer. In this context, overproduction of nitric oxide (NO) attributable to inflammatory stimuli in diseases such as ulcerative colitis and Crohn’s disease may contribute to colonic carcinogenesis. Therefore, we examined the modulation by NO of cytoplasmic ß-catenin levels and the formation of the nuclear ß-catenin/LEF-1 DNA binding complex in conditionally immortalized mouse colonic epithelial cells that differed in adenomatous polyposis coli (Apc) genotype, namely young adult mouse colon (YAMC; Apc^+/+) and immortal mouse colon epithelium (IMCE; Apc^Min/+). Unlike most colon cancer cell lines, this pair of cell lines has either nondetectable or low basal level of ß-catenin when they are cultured under nonpermissive and nonproliferative conditions. Using electrophoretic mobility shift assays, we found that NO-releasing agents (E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide and S-nitroso-N-acetylpenicillamine greatly enhanced the formation of ß-catenin/LEF-1 DNA binding complex in a concentration- and time-dependent fashion in YAMC and IMCE cells. Significantly, IMCE cells showed a markedly greater amount of nuclear ß-catenin/LEF-1 DNA binding complex in response to NO. Super shift by anti-ß-catenin antibody confirmed the presence of ß-catenin in the complex. Western blot analysis of the soluble cytoplasmic fractions demonstrated that these NO donors caused differential accumulation of cytoplasmic ß-catenin in YAMC and IMCE. In conclusion, this study indicates that the defective ß-catenin degradation machinery attributable to Apc^Min/+ mutation in IMCE cells not only affects basal levels but also contributes to NO-induced dysregulation of cytoplasmic ß-catenin and nuclear ß-catenin/LEF-1 DNA binding complex formation.

This article has been cited by other articles:

				J. I. Fenton and N. G. Hord Stage matters: choosing relevant model systems to address hypotheses in diet and cancer chemoprevention research Carcinogenesis, May 1, 2006; 27(5): 893 - 902. [Abstract] [Full Text] [PDF]

				N. P.Y. Lee, D. D. Mruk, C.-h. Wong, and C. Y. Cheng Regulation of Sertoli-Germ Cell Adherens Junction Dynamics in the Testis Via the Nitric Oxide Synthase (NOS)/cGMP/Protein Kinase G (PRKG)/{beta}-Catenin (CATNB) Signaling Pathway: An In Vitro and In Vivo Study Biol Reprod, September 1, 2005; 73(3): 458 - 471. [Abstract] [Full Text] [PDF]

				J. M. Mei, G. L. Borchert, S. P. Donald, and J. M. Phang Matrix metalloproteinase(s) mediate(s) NO-induced dissociation of {beta}-catenin from membrane bound E-cadherin and formation of nuclear {beta}-catenin/LEF-1 complex Carcinogenesis, December 1, 2002; 23(12): 2119 - 2122. [Abstract] [Full Text] [PDF]

				A. Thiele, M. Wasner, C. Muller, K. Engeland, and S. Hauschildt Regulation and Possible Function of {beta}-Catenin in Human Monocytes J. Immunol., December 15, 2001; 167(12): 6786 - 6793. [Abstract] [Full Text] [PDF]

				X. P. Hao, T. G. Pretlow, J. S. Rao, and T. P. Pretlow {beta}-Catenin Expression Is Altered in Human Colonic Aberrant Crypt Foci Cancer Res., November 1, 2001; 61(22): 8085 - 8088. [Abstract] [Full Text] [PDF]

				C. D. Mao, P. Hoang, and P. E. DiCorleto Lithium Inhibits Cell Cycle Progression and Induces Stabilization of p53 in Bovine Aortic Endothelial Cells J. Biol. Chem., July 6, 2001; 276(28): 26180 - 26188. [Abstract] [Full Text] [PDF]