Expression of Tcf-4, MMP7 and Survivin in Colorectal Cancer and Its Clinical Significance
Abstract
To explore the clinical and pathological significance and correlations among the expressions of Tcf-4, MMP7 and survivin in colorectal cancer. Methods The expressions of Tcf-4, MMP7 and survivin mRNA in tumor tissues and adjacent normal mucosa from 50 colorectal cancer patients were detected by reverse transcription PCR (RT-PCR). The expressed proteins of Tcf-4, MMP7 and survivin were measured using immunohistochemistry staining technique (Elivision) in 100 colorectal cancer samples and 60 normal mucosa tissue samples. We analyzed the correlations between those measurements and their associations with clinical and pathological characteristics. Results Positive expressions of Tcf-4, MMP7 and survivin mRNA were found in both cancer and adjacent mucosa tissues, despite a higher level of expression in the cancer tissues (P<0. 01). Expressed proteins were detected in cancer tissues of 69. 00% (69/100)of those with a positive Tcf-4 expression, 77. 00% (77/100)of those with a positive MMP7 expression, and 65. 00% (65/100)of those with a positive survivin expression. Compared with cancer tissues, lower levels of protein expression were found in normal mucosa tissues С16. 67% (10/60) for Tcf-4, 13. 33% (8/60) for MMP7 and 15.00% (9/60) for survivin, P<0. 01}. The expressions of Tcf-4, MMP7 and survivin were all associated with lymphatic metastasis and Dukes staging (P< 0.05). MMP7 expression was associated with depth of tumor invasion (P< 0. 05). Survivin expression was associated with tumor differentiation. The Spearman rank correlation analyses showed that protein expressions in colorectal cancer tissues in those with a positive Tcf-4 were correlated with those with a positive MMP7 (r= 0. 302) and those with a positive survivin (r= 0. 279) (P<0. 01), but not in those with a positive MMP7 and those with a positive survivin (r=0. 097,P>0. 05). Conclusion The expression levels of Tcf-4, MMP7 and survivin are high in colorectal cancer, all being linked to lymph node metastasis and Dukes stages of patients. This suggests that they may be involved in the occurrence» development, malignant growth and clinical progression of colorectal cancer.
Keywords: Colorectal cancer, Immunohistochemistry RT-PCR, Tcf-4 MMP7, Survivin
Full Text:
PDFReferences
Jemal A, Siegel R, Ward E, etal. Cancer statirtics, 2007. CA Cancer J Clin,2007;57(1):43-66.
Heasley LE, Han SY. JNK regulation of oncogenesis. Mol Cells,2006;21(2): 167-173.
Bryja V. Cajanek L, Grahn A, etal. Inhibition of endocytosis blocks Wnt signaling to beta-catenin by promoting disheveled degradation. Acta Physiol (Oxf) ,2007; 190< 1): 55-61.
Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC —/— colon carcinoma. Science, 1997;275(5307); 1784-1787. Fasolini M, Wu X, Flocco M, et al. Hot spots in Tcfl for the interaction with beta-catenin. J Biol Chem. 2003; 278 ( 23 ); 21092-21098.
Roose J, Clevers H. TCF transcription factors; molecular switches in carcinogenesis. Biochim Biophys Acta, 1999; 1424 (2-3): M23-M27.
Ma B« Zhong L, van Blitterswijk CA, et al. T cell factor 4 is a pro-catabolic and apoptotic factor in human articular chondrocytes by potentiating nuclear factor кВ signaling. J Biol Chem, 2013; 288( 24): 17552-17558.
Varro A, Kenny S, Hemers E, et al. Increased gastric expression of MMP7 in hypergastrin emia and significance for epithelial-mesenchymal signaling. Am J Phisiol Gastrointest Liver Physio,2007;292(4): 1133-1140.
Ambrosini G, Adida C, Altieri IX, A novel anti-apopt osis gene, survivin, expressed in cancer and lymphoma. Nat Med, 1997;3(8):917-921.
Kawaski H. Toyoda M, Shinohara H, et al. Expression of survivin correlates with apoptosis, proliferation. and angiogenesis during human colorectal tumorigenesis. Cancer. 2001;91(11);2026-2032.
Amit S, Hatzubai A, Birman Y, et al. Axin-mediated CKI phosphorylation of beta- catenin at Ser 45; a molecular switch for the Wnt pathway. Genes,2002; 16(9); 1066-1076.
GofukuJ, Shiozaki H, Tsujinaka T, et al. Expression of E- cadherin and alpha-cateninin patients with colorectal carcinoma. Correlation with cancer invasion and metastasis. Am J Clin Pathol. 1999; 11 l(l):29-37.
Poy F, Lepourcelet M. Shivdasani RA, et al. Structure of a human Tcf4-beta-catenin complex. Nat Struct Biol. 2001; 8 (12):1053-1057.
Hurlstone A. Clevers H. T-cell factors; turn-ons and turn¬offs. EMBO J . 2002; 21 (10): 2303-2311.
Wang JF. Zhou ZG, Wu DC. Association of T cell factor-4 mRNA expression with clinicopathological characteristics of colorectal cancer. Chinese-German Journal of Clinical Oncology,2008; 7( 10): 584-586
Knox JD, Boreham DR, Walker JA, et al. Mapping of the metalloproteinase gene matrilysin ( MMP7 ) to human chromosome llq21-*-q22. Cytogenet Cell Genet. 1996; 72 ( 2- 3):179-182.
Bucan V, Mandel K, Bertram C, et al. LEF-1 regulates proliferation and MMP-7 transcription in breast cancer cells. Genes Cells,2012; 17(7) ;559-567.
Cheng S, Eliaz I. Lin J, et al. Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7. Int J Oncol, 2013; 42 (6):1869-1874.
Jeffery N, McLean MH. El-Omar EM, et al. The matrix metalloproteinase/tissue inhibitor of matrix metalloproteinase profile in colorectal polyp cancers. Histopathology, 2009; 54 (7);820-828.
Brabletz T, Jung A, Dag S, et al. beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol. 1999 ; 155(4) ; 1033-1038.
Pierre M, Dehertogh В, Gaigneaux A, et al. Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells. BMC Cancer, 2010; 10(1 ): 176. doi; 10. 1186/1471-2407-10- 176.
Pryczynicz A, Gryko M. Niewiarowska K, et al. Immunohistochemical expression of MMP-7 protein and its serum level in colorectal cancer. Folia Histochem Cytobiol, 2013;51(3);206-212.
Refbacks
- There are currently no refbacks.
