Comparative characteristics of the transcriptional activity of CDH1, CTNNB1 genes and the expression levels of E-cadherin, β-catenin proteins, coded by these genes, in intestinal-type gastric adenocarcinoma

Authors

  • V. A. Tumanskiy Zaporizhzhia State Medical University,
  • T. A. Khrystenko Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1237.2017.1.97490

Keywords:

gastric cancer, adenocarcinoma, CTNNB1 protein, human, CDH1 protein, beta Catenin, E-Cadherin

Abstract

Molecular genetics abnormalities, underlying aberrant expression of E-cadherin and β-catenin in malignant tumors, are still unclear.

Aim: to compare the mRNA expression levels of CDH1 and CTNNB1 genes and the immunohistochemical expression levels of E-cadherin and β-catenin proteins in intestinal-type gastric adenocarcinoma.

Materials and methods. The molecular genetic (real-time PCR) and immunohistochemical studies of the intestinal-type gastric adenocarcinoma (30 patients; I, II and III clinical stages were included) and of the normal stomach mucosa (10 samples) were conducted.

Results. In comparison with the normal stomach mucosa, the intestinal-type gastric adenocarcinoma differs by the reduced transcriptional activity of the CDH1 gene [Me of relative normalized ratio of mRNA expression level is 0.14 (0.03; 0.40)], which correlates with the low expression level of E-cadherin in cancer cells [Me is 27,59 CUOD (23,14; 37,19), Spearman's correlation coefficient = 0,73], and also by the heightened transcriptional activity of the CTNNB1 gene [Me of relative normalized ratio of mRNA expression level is 4.32 (2.11; 11.43)], which correlates with the high expression level of β-catenin in cancer cells [Me is 116.65 CUOD (110.34; 151.32), Spearman's correlation coefficient = 0,94]. There is a reverse correlation between the CDH1 mRNA expression level and the degree of histological differentiation of intestinal-type gastric adenocarcinoma (correlation coefficient γ = -0,44); there is a direct correlation between the CTNNB1 and CDH1 mRNA expression levels (only for the I clinical stage cases); there are a direct correlations between the E-cadherin and β-catenin expression levels, and also between the CTNNB1 mRNA expression level and the E-cadherin expression level (only for the I-II clinical stage cases).

Conclusion. The data indicate that decrease of transcriptional activity of the CDH1 gene and E-cadherin expression level, and also increase of transcriptional activity of the CTNNB1 gene and β-catenin expression level in the cancer cells play a critical role in the process of progression of intestinal-type gastric adenocarcinoma.

References

Sun, G., Wu, J., Wu, J., Pan, Y., & Jin, R. (2012) Caveolin-1, E-cadherin and β-catenin in Gastric Carcinoma, Precancerous Tissues and Chronic Non-atrophic Gastritis. Chinese Journal of Cancer Research, 24, 23–28. doi: 10.1007/s11670-012-0023-0.

Liu, X., & Chu, K. (2014) E-Cadherin and Gastric Cancer: Cause, Consequence, and Applications. BioMed Research International, 2014, 89–98. doi: 10.1155/2014/637308.

Carneiro, P., Fernandes, M. S., Figueiredo, J., Caldeira, J., Carvalho, J., Pinheiro, H., et al. (2012) E-cadherin dysfunction in gastric cancer – cellular consequences, clinical applications and open questions. FEBS Letters, 586(18), 2981–9.

Zali, M. R., Moaven, O., Asadzadeh Aghdaei, H., Ghafarzadegan, K., Ahmadi, K. J., Farzadnia, M., et al. (2009) Clinicopathological significance of E-cadherin, b-catenin and p53 expression in gastric adenocarcinoma. Journal of Research in Medical Sciences, 14, 239–247.

Li, L. F., Wei, Z. J., Sun, H., & Jiang, B. (2014) Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis. World Journal of Gastroenterology, 20(34), 12313–12321. doi: 10.3748/wjg.v20.i34.12313

Yu, X. W., Xu, Q., Xu, Y., Gong, Y. H., & Yuan, Y. (2014) Expression of the E-cadherin/β-catenin/tcf-4 pathway in gastric diseases with relation to Helicobacter pylori infection: clinical and pathological implications. Asian Pacific Journal of Cancer Prevention, 15(1), 215–20. doi : 10.7314/APJCP.2014.15.1.215.

Sobin, L. H., Gospodarowicz, M. K., & Wittekind, C. (2009) International Union Against Cancer (UICC). TNM Classification of Malignant Tumours. New York: Wiley-Blackwell.

Dabbs, D. J. (Ed.) (2010). Diagnostic Immunohistochemistry. Philadelphia: Saunders/Elsevier.

Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., & Zubko, M. D. (patentee) (2015) Patent Ukrainy na korysnu model №9 9314 Ukraina, MPK (2015) G01N 21/00, G06K 9/00. Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparativ [Ukraine patent for utility model №99314 Ukraine, IPC (2015) G01N 21/00, G06K 9/00. Method of photo digital morphometrical study of immunohistochemical micropreparations]. Biuleten, 10. [in Ukrainian].

Rasband, W. S. (1997–2016) Image. J. Bethesda, Maryland. Retrived from: http://imagej.nih.gov/ij/

Chan, A. O. (2006) E-cadherin in gastric cancer. World Journal of Gastroenterology, 12(2), 199–203. doi: 10.3748/wjg.v12.i2.199.

Korpal, M., Lee, E. S., Hu, G., & Kang, Y. (2008) The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. The Journal of Biological Chemistry, 283(22), 14910–14914. doi: 10.1074/jbc.C800074200.

Park, S. M., Gaur, A. B., Lengyel, E., & Peter, E. M. (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development, 22(7), 894–907. doi: 10.1101/gad.1640608.

Carvalho, J., van Grieken, N. C., Pereira, P. M., Sousa, S., Tijssen, M., Buffart, T. E., et al. (2012) Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer. The Journal of Pathology, 228(1), 31–44. doi: 10.1002/path.4032.

Suriano, G., Vrcelj, N., Senz J., Ferreira, P., Masoudi, H., Cox, K., et al. (2005) b-Catenin (CTNNB1) Gene Amplification: A New Mechanism of Protein Overexpression in Cancer. Genes, Chromosomes and Cancer, 42, 238–46. doi: 10.1002/gcc.20135.

Lins, R. R., Oshima, C. T., de Oliviera, L. A., Silva, M. S., Mader, A. M., & Waisberg, G. (2016) Expression of E-cadherin and WNT-pathway proteins β-catenin, APC, TCF-4 and surviving in gastric adenocarcinoma: clinical and pathological implication. Arquivos Brasileiros de Cirurgia Digestiva (São Paulo), 29, 227–231. doi: 10.1590/0102-6720201600040004.

Isaeva, A. V., Zima, A. P., Shabalova, I. P., Ryazantseva, N. V., Vasil'eva, O. A., Kasoayn, K. T., et al. (2015) β-Katenin: struktura, funkcii i rol' v opukholevoj transformacii e'pitelial'nykh kletok [SS-catenin: structure, function and role in malignant transformation of epithelial cells]. Vestnik Rossijskoj akademii medicinskikh nauk, 70(4), 475–483. [in Russian].

Aparicio, L. A., Valladares, M., Blanco, M., Alonso, G., & Figueroa, A. (2012) Biological influence of Hakai in cancer: a 10-year review. Cancer and Metastasis Reviews, 31(1), 375–386. doi: 10.1007/s10555-012-9348-x.

Xing, X., Tang, Y. B., Yuan, G., Wang, Y., Wang, J., Yang, Y., & Chen, M. (2013) The prognostic value of E-cadherin in gastric cancer: A meta-analysis. International Journal of Cancer, 132, 2589–2596. doi: 10.1002/ijc.27947.

How to Cite

1.
Tumanskiy VA, Khrystenko TA. Comparative characteristics of the transcriptional activity of CDH1, CTNNB1 genes and the expression levels of E-cadherin, β-catenin proteins, coded by these genes, in intestinal-type gastric adenocarcinoma. Pathologia [Internet]. 2017Apr.7 [cited 2024Jul.18];(1). Available from: http://pat.zsmu.edu.ua/article/view/97490

Issue

Section

Original research