Features of CDH1, CTNNB1 genes transcriptional activity and expression levels of E-cadherin, β-catenin proteins coded by these genes on the I, II, III, IV stages of colorectal adenocarcinoma development

Authors

  • M. A. Shyshkin Zaporizhzhіa State Medical University, Ukraine,
  • V. O. Tumanskyi Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2018.2.141432

Keywords:

colorectal cancer, CTNNB1 human protein, CDH1 human protein, beta catenin, E-cadherin

Abstract

Aim – analysis of CDH1 and CTNNB1 genes mRNA expression levels and expression levels of E-cadherin, β-catenin proteins coded by these genes, and also their correlations with KRAS gene transcriptional activity level on the I, II, III, IV stages (pTNM) of colorectal adenocarcinoma (CRA) development.

Materials and methods. Parallel immunohistochemical and molecular-genetic, pathohistological studies of operational material of CRA from 40 patients (4 study groups – I, II, III, IV stages according to pTNM classification – 10 cases in each group) with diagnosis of colorectal adenocarcinoma, and sectional material of 10 fragments of distal colonic wall with normal histological structure were conducted.

Results. In comparison with unchanged mucosa of distal colon CRA is characterized by the decreased CDH1 gene transcriptional activity. There is the tendency to reducing of CDH1 gene mRNA expression in the study groups – from the I to the IV stages of the tumor development. CRA is characterized by the low E-cadherin expression level, which also has the tendency to reducing in the study groups. Moreover, in comparison with unchanged mucosa of distal colon CRA is characterized by the increased CTNNB1 gene transcriptional activity and the high β-catenin expression level. There aren’t statistically significant differences between the CTNNB1 gene mRNA, β-catenin expression levels in the study groups. There are direct correlations between the expression levels of the studied genes and the molecules, coded by these genes, and also reverse correlations between the KRAS and CDH1 genes mRNA expression levels, the KRAS gene mRNA expression level and the E-cadherin expression level, direct correlation between the KRAS gene mRNA expression level and the β-catenin expression level.

Conclusions. CRA is characterized by the decreased CDH1 gene transcriptional activity that correlates with the low E-cadherin expression level, and by the increased CTNNB1 gene transcriptional activity that correlates with the high β-catenin expression level. The CDH1 gene transcriptional activity and the expression level of E-cadherin, which is coded by this gene, decrease during the CRA progression from the I to the IV stages. CRA is characterized by reverse correlations between the KRAS and CDH1 genes mRNA expression levels, the KRAS gene mRNA expression level and the E-cadherin expression level, direct correlation between the KRAS gene mRNA expression level and the β-catenin expression level.

 

References

Church J. (2016) Molecular genetics of colorectal cancer. Seminars in Colon and Rectal Surgery, 27 (4), 172-175.

Christou, N., Perraud, A., Blondy, S., Jauberteau, M.-O., Battu, S., Mathonnet, M. (2017) E-cadherin: A potential biomarker of colorectal cancer prognosis. Oncology Letters, 13 (6), 4571-4576.

Wong, S.H.M., Fang, C.M., Chuah, L.H., Leong, C.O., Ngai, S.C. (2018) E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Critical Reviews in Oncology/Hematology, 121, 11-22.

Chen, X., Wang, Y., Xia, H., Wang, Q., Jiang, X., Lin, Z., Ma, Y., Yang, Y., Hu, M. (2012) Loss of E-cadherin promotes the growth, invasion and drug resistance of colorectal cancer cells and is associated with liver metastasis. Molecular Biology Reports, 39 (6), 6707-6714.

Lu, M.H., Huang, C.C., Pan, M.R., Chen, H.H., Hung, W.C. (2012) Prospero homeobox 1 promotes epithelial-mesenchymal transition in colon cancer cells by inhibiting E-cadherin via miR-9. Clinical Cancer Researches, 18 (23), 6416-6425.

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 opuk¬holevoj 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].

Morin, P.J., Kinzler, K.W., Sparks, A.B. (2016) β-Catenin Mutations: Insights into the APC Pathway and the Power of Genetics. Cancer Research, 76 (19), 5587-5589.

Bourroul, G.M., Fragoso, H.J., Gomes, J.W., Bourroul, V.S., Oshima, C.T., Gomes, T.S., Saba, G.T., Palma, R.T., Waisberg, J. (2016) The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma. Einstein (San Paulo), Vol.14 (2), 135-42.

Yoshida, N., Kinugasa, T., Ohshima, K., Yuge, K., Ohchi, T., Fujino, S., Shiraiwa, S., Katagiri, M., Akagi, Y. (2015) Analysis of Wnt and β-catenin Expression in Advanced Colorectal Cancer. Anticancer Research, 35 (8), 4403-10.

Boutin, A.T., Liao, W.T., Wang, M., Hwang S.S., Karpinets, T.V., Cheung, H., et al. (2017) Oncogenic Kras drives invasion and maintains metastases in colorectal cancer. Genes & Development, 31(4), 370–382.

Manzi, J. P. (Ed.) (2015). Exploring cancer proliferative signaling pathways. Boston: ThermoFisher SCIENTIFIC.

Lemieux, E., Cagnol, S., Beaudry, K., Carrier, J., Rivard, N. (2015) Oncogenic KRAS signalling promotes the Wnt/β-catenin pathway through LRP6 in colorectal cancer. Oncogene, 34 (38), 4914-4927.

Sobin, L. H., Gospodarowicz, M. K., Wittekind, C. International Union Against Cancer (UICC): TNM Classification of Malignant Tumours. New York: Wiley-Blackwell, 2009, 50 pp.

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/.

He, X., Chen, Z., Jia, M. (2013) Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis. PLoS One, 8 (7), 70858.

Buda, A., Pignatelli, M. (2011) E-cadherin and the cytoskeletal network in colorectal cancer development and metastasis. Cell Communication & Adhesion, 18 (6), 133-143.

Kim, S.A., Inamura, K., Yamauchi, M., Nishihara, R., Mima, K., Sukawa, Y., Li, T., Yasunari, M., Morikava, T., Fitzherald, K.C., Fuchs, C.S., Wu, K., Chan, A.T., Zhang, X., Ogino, S., Qian, Z.R. (2016) Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis. British Journal of Cancer, 114 (2), 199-206.

Bruun, J., Kolberg, M., Nesland, J.M., Svindland, A., Nesbakken, A., Lothe, R.A. (2014) Prognostic Significance of β-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series. Frontiers in Oncology, 21 (4), 118-120.

Shyshkin, M.A. (2018) Molekulyarno-immunogistohimicheskaya harakteristika proliferatsii i apoptoza opuholevyih kletok kolorektalnoy adenokartsinomyi [Molecular-immunohistochemical characteristics of proliferation and apoptosis of tumor cells in colorectal adenocarcinoma]. Pathologia, 15 (1), 49–56. [in Russian].

Nakamoto, K., Nagahara, H., Maeda, K., Noda, E., Inoue, T., Yashiro, M., Nishiguchi, Y., Ohira, M., Hirakawa, K. (2013) Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer. Oncology Letters, 5 (4), 1295-1300.

How to Cite

1.
Shyshkin MA, Tumanskyi VO. Features of CDH1, CTNNB1 genes transcriptional activity and expression levels of E-cadherin, β-catenin proteins coded by these genes on the I, II, III, IV stages of colorectal adenocarcinoma development. Pathologia [Internet]. 2018Sep.12 [cited 2024Apr.19];(2). Available from: http://pat.zsmu.edu.ua/article/view/141432

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Section

Original research