Carcinogenesis, Vol. 23, No. 1, 87-91,
January 2002
© 2002 Oxford University Press
CANCER BIOLOGY |
Increased ß-catenin mRNA levels and mutational alterations of the APC and ß-catenin gene are present in intestinal-type gastric cancer
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, D-39120 Magdeburg,
1 Max-Planck-Institute for Molecular Physiology, D-44202 Dortmund, Germany and
2 Department of Medicine & Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong
ß-Catenin is critical for intercellular adhesion and also plays a role as a transcription activating protein in the Wnt signalling pathway. Increased protein levels and mutation of the ß-catenin gene have been demonstrated in various cancers; however, the role of ß-catenin in gastric cancer remains largely unknown. Using gastric cancer tissues and normal adjacent gastric mucosa obtained from 20 patients with gastric cancer (eight diffuse-type, 12 intestinal-type) undergoing gastric resection or endoscopy, we assessed the expression of ß-catenin by immunohistochemistry and quantitative PCR analysis. Furthermore, the tumour suppressor gene APC, which down-regulates the ß-catenin levels was analysed for mutations. Overall mRNA levels of ß-catenin were significantly increased in the tumour samples compared with the matched normal gastric mucosa (P < 0.05). Increased ß-catenin mRNA levels were significantly more frequent in intestinal-type gastric cancers as compared to diffuse-type gastric cancers (P < 0.01). Six out of 20 tumours exhibited >6-fold increased ß-catenin mRNA levels as compared with normal mucosa. APC gene mutations were found in four cases. A ß-catenin gene mutation was identified only in one intestinal-type gastric cancer exhibiting a massive overexpression of ß-catenin mRNA in the tumour. In intestinal-type gastric cancers ß-catenin mRNA levels are greatly enhanced. APC and ß-catenin gene mutations are also present primarily in intestinal-type gastric cancers. These findings support the hypothesis that in intestinal-type gastric cancers the accumulation of ß-catenin protein may result from impaired degradation of the ß-catenin protein due to alterations of the ß-catenin and APC genes, as well as from enhanced ß-catenin transcription which is present in the great majority of intestinal-type gastric cancers.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Burgermeister, X. Xing, C. Rocken, M. Juhasz, J. Chen, M. Hiber, K. Mair, M. Shatz, M. Liscovitch, R. M. Schmid, et al. Differential Expression and Function of Caveolin-1 in Human Gastric Cancer Progression Cancer Res., September 15, 2007; 67(18): 8519 - 8526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tomita, Y. Yamada, T. Oyama, K. Hata, Y. Hirose, A. Hara, T. Kunisada, Y. Sugiyama, Y. Adachi, H. Linhart, et al. Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the {beta}-Catenin/Tcf Signaling Pathway Cancer Res., May 1, 2007; 67(9): 4079 - 4087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lowy, W. M. Clements, J. Bishop, L. Kong, T. Bonney, K. Sisco, B. Aronow, C. Fenoglio-Preiser, and J. Groden {beta}-Catenin/Wnt Signaling Regulates Expression of the Membrane Type 3 Matrix Metalloproteinase in Gastric Cancer. Cancer Res., May 1, 2006; 66(9): 4734 - 4741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wei, W. Gong, M. Kanai, C. Schlunk, L. Wang, J. C. Yao, T.-T. Wu, S. Huang, and K. Xie Drastic Down-regulation of Kruppel-Like Factor 4 Expression Is Critical in Human Gastric Cancer Development and Progression Cancer Res., April 1, 2005; 65(7): 2746 - 2754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, C. Rocken, C. Lofton-Day, H.-U. Schulz, O. Muller, N. Kutzner, P. Malfertheiner, and M. P.A. Ebert Molecular analysis of APC promoter methylation and protein expression in colorectal cancer metastasis Carcinogenesis, January 1, 2005; 26(1): 37 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P.A. Ebert, J. Yu, J. Hoffmann, A. Rocco, C. Rocken, S. Kahmann, O. Muller, M. Korc, J. J. Sung, and P. Malfertheiner Loss of Beta-Catenin Expression in Metastatic Gastric Cancer J. Clin. Oncol., May 1, 2003; 21(9): 1708 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nabais, J. C. Machado, C. Lopes, R. Seruca, F. Carneiro, and M. Sobrinho-Simoes Patterns of {beta}-Catenin Expression in Gastric Carcinoma: Clinicopathological Relevance and Mutation Analysis International Journal of Surgical Pathology, January 1, 2003; 11(1): 1 - 9. [Abstract] [PDF]
|
|