| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo 104, Japan
ß-Catenin is a key regulator of the cadherin-mediated cell-cell adhesion system and an important element in the Wnt signal transduction pathway. Stabilization and accumulation of cytoplasmic ß-catenin, which result from mutations in either the adenomatous polyposis coli or ß-catenin genes, are causatively associated with colon carcinogenesis. In the present study, we examined the expression of ß-catenin in rat colon tumors induced by azoxymethane in comparison with adjacent normal colon mucosa by immunostaining and immunoblotting. Cytoplasmic and nuclear immunostaining was pronounced in all colon adenoma and carcinoma tissues, whereas antibody binding was limited to membranes at the intercellular borders in normal colon epithelial cells. Increase of the free ß-catenin fraction in tumor cells was also indicated by immunoblot analysis of fractionated tissue lysates. Investigation of mutations in the glycogen synthase kinase-3ß phosphorylation consensus motif of the ß-catenin gene by PCR-single strand conformation polymorphism methods and direct sequencing revealed eight mutations in six of the eight colon carcinomas, and seven of these were shown to be G:C to A:T transitions, with five being CTGGA to CTGAA. Such frequent mutations of the ß-catenin gene in azoxymethane-induced rat colon tumors suggest that consequent alterations in the stability and localization of the protein may play an important role in this colon carcinogenesis model.
1 This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan, and a grant from the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&G Promotion, and Product Review of Japan.
2 To whom requests for reprints should be addressed, at Cancer Prevention Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan.
Received 10/21/97. Accepted 11/11/97.
This article has been cited by other articles:
|
|
 |
|
  H. Xiao, X. Hao, B. Simi, J. Ju, H. Jiang, B. S. Reddy, and C. S. Yang Green tea polyphenols inhibit colorectal aberrant crypt foci (ACF) formation and prevent oncogenic changes in dysplastic ACF in azoxymethane-treated F344 rats Carcinogenesis, January 1, 2008; 29(1): 113 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhang, A. Ma, S. J. Urbanski, and D.-M. McCafferty Induction of inducible nitric oxide synthase: a protective mechanism in colitis-induced adenocarcinoma Carcinogenesis, May 1, 2007; 28(5): 1122 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mezhybovska, K. Wikstrom, J. F. Ohd, and A. Sjolander The Inflammatory Mediator Leukotriene D4 Induces beta-Catenin Signaling and Its Association with Antiapoptotic Bcl-2 in Intestinal Epithelial Cells J. Biol. Chem., March 10, 2006; 281(10): 6776 - 6784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shoji, M. Takahashi, N. Takasuka, N. Niho, T. Kitamura, H. Sato, T. Maruyama, Y. Sugimoto, S. Narumiya, T. Sugimura, et al. Prostaglandin E receptor EP3 deficiency modifies tumor outcome in mouse two-stage skin carcinogenesis Carcinogenesis, December 1, 2005; 26(12): 2116 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ju, J. Hong, J.-n. Zhou, Z. Pan, M. Bose, J. Liao, G.-y. Yang, Y. Y. Liu, Z. Hou, Y. Lin, et al. Inhibition of Intestinal Tumorigenesis in Apcmin/+ Mice by (-)-Epigallocatechin-3-Gallate, the Major Catechin in Green Tea Cancer Res., November 15, 2005; 65(22): 10623 - 10631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Currier, S. E. Solomon, E. G. Demicco, D. L. F. Chang, M. Farago, H. Ying, I. Dominguez, G. E. Sonenshein, R. D. Cardiff, Z.-X. J. Xiao, et al. Oncogenic Signaling Pathways Activated in DMBA-Induced Mouse Mammary Tumors Toxicol Pathol, October 1, 2005; 33(6): 726 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Paulsen, E. M. Loberg, H. B. Olstorn, H. Knutsen, I.-L. Steffensen, and J. Alexander Flat Dysplastic Aberrant Crypt Foci Are Related to Tumorigenesis in the Colon of Azoxymethane-Treated Rat Cancer Res., January 1, 2005; 65(1): 121 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tanaka, R. Suzuki, H. Kohno, S. Sugie, M. Takahashi, and K. Wakabayashi Colonic adenocarcinomas rapidly induced by the combined treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate in male ICR mice possess {beta}-catenin gene mutations and increases immunoreactivity for {beta}-catenin, cyclooxygenase-2 and inducible nitric oxide synthase Carcinogenesis, January 1, 2005; 26(1): 229 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kawamori, Y. Totsuka, N. Uchiya, T. Kitamura, H. Shibata, T. Sugimura, and K. Wakabayashi Carcinogenicity of aminophenylnorharman, a possible novel endogenous mutagen, formed from norharman and aniline, in F344 rats Carcinogenesis, October 1, 2004; 25(10): 1967 - 1672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fujiwara, M. Ochiai, T. Ohta, M. Ohki, H. Aburatani, M. Nagao, T. Sugimura, and H. Nakagama Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Carcinogenesis, August 1, 2004; 25(8): 1495 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Imai, J.-I. Onose, M. Hasumura, M. Ueda, T. Takizawa, and M. Hirose Sequential Analysis of Development of Invasive Thyroid Follicular Cell Carcinomas in Inflamed Capsular Regions of Rats Treated with Sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation Toxicol Pathol, February 1, 2004; 32(2): 229 - 236. [Abstract] [PDF]
|
|
|
|
|
|
Y. Yamada and H. Mori Pre-cancerous lesions for colorectal cancers in rodents: a new concept Carcinogenesis, June 1, 2003; 24(6): 1015 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamada, T. Oyama, Y. Hirose, A. Hara, S. Sugie, K. Yoshida, N. Yoshimi, and H. Mori {beta}-Catenin mutation is selected during malignant transformation in colon carcinogenesis Carcinogenesis, January 1, 2003; 24(1): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirose, T. Kuno, Y. Yamada, K. Sakata, M. Katayama, K. Yoshida, Z. Qiao, K. Hata, N. Yoshimi, and H. Mori Azoxymethane-induced beta-catenin-accumulated crypts in colonic mucosa of rodents as an intermediate biomarker for colon carcinogenesis Carcinogenesis, January 1, 2003; 24(1): 107 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Koesters, M. A. Hans, A. Benner, R. Prosst, J. Boehm, J. Gahlen, and M. von Knebel Doeberitz Predominant mutation of codon 41 of the {beta}-catenin proto-oncogene in rat colon tumors induced by 1,2-dimethylhydrazine using a complete carcinogenic protocol Carcinogenesis, November 1, 2001; 22(11): 1885 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ochiai, T. Ubagai, T. Kawamori, H. Imai, T. Sugimura, and H. Nakagama High susceptibility of Scid mice to colon carcinogenesis induced by azoxymethane indicates a possible caretaker role for DNA-dependent protein kinase Carcinogenesis, September 1, 2001; 22(9): 1551 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Erik Paulsen, I.-L. Steffensen, E. M. Loberg, T. Husoy, E. Namork, and J. Alexander Qualitative and Quantitative Relationship between Dysplastic Aberrant Crypt Foci and Tumorigenesis in the Min/+ Mouse Colon Cancer Res., July 1, 2001; 61(13): 5010 - 5015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W A Brown, S A Skinner, C Malcontenti-Wilson, D Vogiagis, and P E O'Brien Non-steroidal anti-inflammatory drugs with activity against either cyclooxygenase 1 or cyclooxygenase 2 inhibit colorectal cancer in a DMH rodent model by inducing apoptosis and inhibiting cell proliferation Gut, May 1, 2001; 48(5): 660 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Groos, E. Reale, and L. Luciano Re-evaluation of Epoxy Resin Sections for Light and Electron Microscopic Immunostaining J. Histochem. Cytochem., March 1, 2001; 49(3): 397 - 406. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Yamada, N. Yoshimi, Y. Hirose, K. Matsunaga, M. Katayama, K. Sakata, M. Shimizu, T. Kuno, and H. Mori Sequential Analysis of Morphological and Biological Properties of {beta}-Catenin-accumulated Crypts, Provable Premalignant Lesions Independent of Aberrant Crypt Foci in Rat Colon Carcinogenesis Cancer Res., March 1, 2001; 61(5): 1874 - 1878. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Naishiro, T. Yamada, A. S. Takaoka, R. Hayashi, F. Hasegawa, K. Imai, and S. Hirohashi Restoration of Epithelial Cell Polarity in a Colorectal Cancer Cell Line by Suppression of {beta}-catenin/T-Cell Factor 4-mediated Gene Transactivation Cancer Res., March 1, 2001; 61(6): 2751 - 2758. [Abstract] [Full Text]
|
|
|
|
|
|
C. A. Blum, M. Xu, G. A. Orner, A. T. Fong, G. S. Bailey, G. D. Stoner, D. T. Horio, and R. H. Dashwood {beta}-Catenin mutation in rat colon tumors initiated by 1,2-dimethylhydrazine and 2-amino-3-methylimidazo[4,5-f]quinoline, and the effect of post-initiation treatment with chlorophyllin and indole-3-carbinol Carcinogenesis, February 1, 2001; 22(2): 315 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y Kishimoto, N Takata, T Jinnai, T Morisawa, G Shiota, H Kawasaki, and J Hasegawa Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane Gut, December 1, 2000; 47(6): 812 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tsujiuchi, M. Tsutsumi, Y. Sasaki, N. Murata, and Y. Konishi Mutations of Adenomatous Polyposis Coli and {beta}-Catenin Genes during Progression of Lung Tumors Induced by N-Nitrosobis(2-hydroxypropyl)amine in Rats Cancer Res., December 1, 2000; 60(23): 6611 - 6616. [Abstract] [Full Text]
|
|
|
|
|
|
M. Iwamoto, D. J Ahnen, W. A. Franklin, and T. H. Maltzman Expression of {beta}-catenin and full-length APC protein in normal and neoplastic colonic tissues Carcinogenesis, November 1, 2000; 21(11): 1935 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Hsu, Y.-M. Jeng, T.-L. Mao, J.-S. Chu, P.-L. Lai, and S.-Y. Peng {beta}-Catenin Mutations Are Associated with a Subset of Low-Stage Hepatocellular Carcinoma Negative for Hepatitis B Virus and with Favorable Prognosis Am. J. Pathol., September 1, 2000; 157(3): 763 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bissonnette, S. Khare, F. C. von Lintig, R. K. Wali, L. Nguyen, Y. Zhang, J. Hart, S. Skarosi, N. Varki, G. R. Boss, et al. Mutational and Nonmutational Activation of p21ras in Rat Colonic Azoxymethane-induced Tumors: Effects on Mitogen-activated Protein Kinase, Cyclooxygenase-2, and Cyclin D1 Cancer Res., August 1, 2000; 60(16): 4602 - 4609. [Abstract] [Full Text]
|
|
|
|
|
|
M. Takahashi, M. Mutoh, T. Kawamori, T. Sugimura, and K. Wakabayashi Altered expression of {beta}-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis Carcinogenesis, July 1, 2000; 21(7): 1319 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamada, N. Yoshimi, Y. Hirose, K. Kawabata, K. Matsunaga, M. Shimizu, A. Hara, and H. Mori Frequent {beta}-Catenin Gene Mutations and Accumulations of the Protein in the Putative Preneoplastic Lesions Lacking Macroscopic Aberrant Crypt Foci Appearance, in Rat Colon Carcinogenesis Cancer Res., July 1, 2000; 60(13): 3323 - 3327. [Abstract] [Full Text]
|
|
|
|
|
|
M. Takahashi, S. Nakatsugi, T. Sugimura, and K. Wakabayashi Frequent mutations of the {beta}-catenin gene in mouse colon tumors induced by azoxymethane Carcinogenesis, June 1, 2000; 21(6): 1117 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Rao, I. Cooma, J. G.R. Rodriguez, B. Simi, K. El-Bayoumy, and B. S. Reddy Chemoprevention of familial adenomatous polyposis development in the APCmin mouse model by 1,4-phenylene bis(methylene)selenocyanate Carcinogenesis, April 1, 2000; 21(4): 617 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Cooper, S. Murthy, K. Kido, H. Yoshitake, and A. Flanigan Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation Carcinogenesis, April 1, 2000; 21(4): 757 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Wali, S. Skarosi, J. Hart, Y. Zhang, M.e. Dolan, R. C. Moschel, L. Nguyen, R. Mustafi, T. A. Brasitus, and M. Bissonnette Inhibition of O6-methylguanine-DNA methyltransferase increases azoxymethane-induced colonic tumors in rats Carcinogenesis, December 1, 1999; 20(12): 2355 - 2360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tsujiuchi, M. Tsutsumi, Y. Sasaki, M. Takahama, and Y. Konishi Different Frequencies and Patterns of {beta}-Catenin Mutations in Hepatocellular Carcinomas Induced by N-Nitrosodiethylamine and a Choline-deficient L-Amino Acid-defined Diet in Rats Cancer Res., August 1, 1999; 59(16): 3904 - 3907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gamallo, J. Palacios, G. Moreno, J. Calvo de Mora, A. Suarez, and A. Armas {beta}-Catenin Expression Pattern in Stage I and II Ovarian Carcinomas : Relationship with {beta}-Catenin Gene Mutations,Clinicopathological Features, and Clinical Outcome Am. J. Pathol., August 1, 1999; 155(2): 527 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mirabelli-Primdahl, R. Gryfe, H. Kim, A. Millar, C. Luceri, D. Dale, E. Holowaty, B. Bapat, S. Gallinger, and M. Redston {beta}-Catenin Mutations Are Specific for Colorectal Carcinomas with Microsatellite Instability but Occur in Endometrial Carcinomas Irrespective of Mutator Pathway Cancer Res., July 1, 1999; 59(14): 3346 - 3351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Samowitz, M. D. Powers, L. N. Spirio, F. Nollet, F. van Roy, and M. L. Slattery {beta}-Catenin Mutations Are More Frequent in Small Colorectal Adenomas Than in Larger Adenomas and Invasive Carcinomas Cancer Res., April 1, 1999; 59(7): 1442 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ogawa, Y. Yamada, K. Kishibe, K. Ishizaki, and Y. Tokusashi {beta}-Catenin Mutations Are Frequent in Hepatocellular Carcinomas but Absent in Adenomas Induced by Diethylnitrosamine in B6C3F1 Mice Cancer Res., April 1, 1999; 59(8): 1830 - 1833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Mahmoud, R. T. Bilinski, M. R. Churchill, W. Edelmann, R. Kucherlapati, and M. M. Bertagnolli Genotype-Phenotype Correlation in Murine Apc Mutation: Differences in Enterocyte Migration and Response to Sulindac Cancer Res., January 1, 1999; 59(2): 353 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. d. L. Coste, B. Romagnolo, P. Billuart, C.-A. Renard, M.-A. Buendia, O. Soubrane, M. Fabre, J. Chelly, C. Beldjord, A. Kahn, et al. Somatic mutations of the beta -catenin gene are frequent in mouse and human hepatocellular carcinomas PNAS, July 21, 1998; 95(15): 8847 - 8851. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
