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BCL-3 and β-catenin signaling and tumor staging in colorectal cancer
Corresponding Author(s) : Changqing Yin
Cellular and Molecular Biology,
Vol. 66 No. 5: Issue 5
Abstract
Colorectal cancer (CBC) is the third most common cancer in men and the second most common cancer in women in the world, as well as the second leading cause of death among the world's cancers. In this study, to identify the genes involved in the CRC clinical outcomes, the expression of B cell leukemia/lymphoma 3 (BCL-3) gene in patients with colorectal cancer was investigated along with serum level of β-catenin. In this study, samples of 23 patients with colorectal cancer were prepared. mRNA was extracted and then cDNA was prepared for evaluation of PCR. Then, with specific primers for the BCL3, a semi-quantitative RT-PCR test was performed. The enzyme-linked immunosorbent assay (ELISA) was used to assess the serum level of β-catenin. In this study, 23 men with an average age of years were included. BCL-3 expression in tumor tissue was significantly higher than its level in healthy tissue (P=0.021). BCL-3 expression at stage 0 of the tumor was significantly lower than at all other stages (P<0.05), and the comparison between the rest of the CRC stages was not significant (P>0.05). The median of serum β-catenin levels in the patients was 32.83 (22.45, 46.09). There was no significant difference in the amount of serum β-catenin between all 5 stages of the disease and in terms of lymph node metastasis. There were no relationships between age, BMI, smoking history, familial CRC history, and BCL-3 or β-catenin serum levels (P>0.05). In this study, the expression of the BCL-3 gene in tumor specimens was high. It can be said that the BCL-3 gene can act as one of the genes involved in colorectal cancer, along with some genes such as β-catenin. While BCL-3 was associated with a higher stage of CRC, β-catenin didn't show such a relationship with CRC.
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- Aran V, Victorino AP, Thuler LC, Ferreira CG. Colorectal cancer: epidemiology, disease mechanisms and interventions to reduce onset and mortality. Clin Colorectal Cancer 2016; 15(3):195"203.
- Schatoff EM, Leach BI, Dow LE. Wnt signaling and colorectal cancer. Curr Colorectal Cancer Rep 2017; 13(2):101"110.
- Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev 2018; 62:50"60.
- Wang J, Shibayama Y, Zhang A, Ohsaki H, Asano E, Suzuki Y, Kushida Y, Kobara H, Masaki T, Wang Z, Nishiyama A. (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations. Br J Cancer 2019; 120(2):229"237.
- Wanitsuwan W, Kanngurn S, Boonpipattanapong T, Sangthong R, Sangkhathat S. Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers. World J Gastroenterol 2008; 14(39):6052"6059.
- Legge DN, Shephard AP, Collard TJ, Greenhough A, Chambers AC, Clarkson RW, Paraskeva C, Williams AC. BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells. Dis Model Mech 2019; 12(3): dmm037697.
- McKeithan TW, Takimoto GS, Ohno H, Bjorling VS, Morgan R, Hecht BK, Dubé I, Sandberg AA, Rowley JD. BCL3 rearrangements and t (14; 19) in chronic lymphocytic leukemia and other B"cell malignancies: A molecular and cytogenetic study. Genes Chromosomes Cancer 1997; 20(1):64"72.
- Chen CY, Lee DS, Yan YT, Shen CN, Hwang SM, Lee ST, Hsieh PC. Bcl3 bridges LIF"STAT3 to Oct4 signaling in the maintenance of Naí¯ve Pluripotency. Stem Cells 2015; 33(12):3468"3480.
- Legge DN, Shephard AP, Collard TJ, Greenhough A, Chambers AC, Clarkson RW, Paraskeva C, Williams AC. BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells. Dis Model Mech 2019; 12(3): dmm037697.
- Büchau AS, MacLeod DT, Morizane S, Kotol PF, Hata T, Gallo RL. Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes. J Invest Dermatol 2009; 129(9):2148"2155.
- Li S, Huang M, Liu Q, Wang D, Wu R, Zhang X, Chen W, Duan L. Serum Expression of β-Catenin Is a Potential Detection Marker in Patients with Colorectal Cancer. Dis Markers 2019; 2019:5070524.
- Obrocea FL, Sajin M, Marinescu EC, Stoica D. Colorectal cancer and the 7th revision of the TNM staging system: review of changes and suggestions for uniform pathologic reporting. Rom J Morphol Embryol 2011; 52(2):537"544.
- Urban BC, Collard TJ, Eagle CJ, Southern SL, Greenhough A, Hamdollah-Zadeh M, Ghosh A, Poulsom R, Paraskeva C, Silver A, Williams AC. BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling. Gut 2016; 65(7):1151"1164.
- Wulczyn FG, Naumann M, Scheidereit C. Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-kappa B. Nature 1992; 358(6387):597"599.
- Valenta T, Hausmann G, Basler K. The many faces and functions of β"catenin EMBO J 2012; 31(12):2714"2736.
- Hatipoglu OF, Yaykasli KO, Dogan M, Yaykasli E, Bender O, Yasar T, Tapan S, Gunduz M. NF-κB and MAPKs are involved in resistin caused ADAMTS-5 induction in Human Chondrocytes. Clin Invest Med 2015; 38(4): E248-E254.
- Chen X, Wang C, Jiang Y, Wang Q, Tao Y, Zhang H, Zhao Y, Hu Y, Li C, Ye D, Liu D. Bcl-3 promotes Wnt signaling by maintaining the acetylation of β-catenin at lysine 49 in colorectal cancer. Signal Transduct Target Ther 2020; 5(1):52.
- Narasipura SD, Henderson LJ, Fu SW, Chen L, Kashanchi F, Al-Harthi L. Role of β-catenin and TCF/LEF family members in transcriptional activity of HIV in astrocytes. J Virol 2012; 86(4):1911"1921.
- Pećina-Å laus N, Kafka A, Lechpammer M. Molecular genetics of intracranial meningiomas with emphasis on canonical Wnt signalling. Cancers (Basel) 2016; 8(7):67.
- Blum CA, Xu M, Orner GA, et al. 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 [published correction appears in Carcinogenesis 2001 Apr;22(4):685]. Carcinogenesis 2001; 22(2):315"320.
- Nelson, R.L. Dietary minerals and colorectal cancer. In: Rowland, I.R. Nutrition, Toxicity and Cancer. CRC Press, London, pp: 1991; 491-515.
- Yamak N, Yaykasli KO, Yilmaz U, Eroz R, Uzunlar AK, Ankaralı H, Sahiner C, Baltaci D. Association Between Survivin Gene Polymorphisms and the Susceptibility to Colon Cancer Development in Turkish Population, Asian Pac J Cancer Prev 2014; 15(20):8963-8967.
- Puvvada SD, Funkhouser WK, Greene K, Deal A, Chu H, Baldwin AS, Tepper JE, O'Neil BH. NF-ć¸B and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer. Oncology 2010; 78(3-4):181"188.
- Collins PE, Kiely PA, Carmody RJ. Inhibition of transcription by B cell Leukemia 3 (Bcl-3) protein requires interaction with nuclear factor κB (NF-κB) p50. J Biol Chem 2014; 289(10):7059"7067.
- Brocke-Heidrich K, Ge B, Cvijic H. BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription. Oncogene 2006; 25(55):7297"7304.
- Taheri Z, Asadzadeh Aghdaei H, Irani S, Modarressi MH, Noormohammadi Z. Clinical Correlation of miR-200c/141 Cluster DNA Methylation and miR-141 Expression with the Clinicopathological Features of Colorectal Primary Lesions/Tumors. Rep Biochem Mol Biol. 2019;8(3):208"215.
- Rezaei FM, Hashemzadeh S, Gavgani RR, Feizi MH, Pouladi N, Kafil HS, Rostamizadeh L, Oskooei VK, Taheri M, Sakhinia E. Dysregulated KDR and FLT1 Gene Expression in Colorectal Cancer Patients. Rep Biochem Mol Biol. 2019;8(3):244"252.
- Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.
References
Aran V, Victorino AP, Thuler LC, Ferreira CG. Colorectal cancer: epidemiology, disease mechanisms and interventions to reduce onset and mortality. Clin Colorectal Cancer 2016; 15(3):195"203.
Schatoff EM, Leach BI, Dow LE. Wnt signaling and colorectal cancer. Curr Colorectal Cancer Rep 2017; 13(2):101"110.
Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev 2018; 62:50"60.
Wang J, Shibayama Y, Zhang A, Ohsaki H, Asano E, Suzuki Y, Kushida Y, Kobara H, Masaki T, Wang Z, Nishiyama A. (Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations. Br J Cancer 2019; 120(2):229"237.
Wanitsuwan W, Kanngurn S, Boonpipattanapong T, Sangthong R, Sangkhathat S. Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers. World J Gastroenterol 2008; 14(39):6052"6059.
Legge DN, Shephard AP, Collard TJ, Greenhough A, Chambers AC, Clarkson RW, Paraskeva C, Williams AC. BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells. Dis Model Mech 2019; 12(3): dmm037697.
McKeithan TW, Takimoto GS, Ohno H, Bjorling VS, Morgan R, Hecht BK, Dubé I, Sandberg AA, Rowley JD. BCL3 rearrangements and t (14; 19) in chronic lymphocytic leukemia and other B"cell malignancies: A molecular and cytogenetic study. Genes Chromosomes Cancer 1997; 20(1):64"72.
Chen CY, Lee DS, Yan YT, Shen CN, Hwang SM, Lee ST, Hsieh PC. Bcl3 bridges LIF"STAT3 to Oct4 signaling in the maintenance of Naí¯ve Pluripotency. Stem Cells 2015; 33(12):3468"3480.
Legge DN, Shephard AP, Collard TJ, Greenhough A, Chambers AC, Clarkson RW, Paraskeva C, Williams AC. BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells. Dis Model Mech 2019; 12(3): dmm037697.
Büchau AS, MacLeod DT, Morizane S, Kotol PF, Hata T, Gallo RL. Bcl-3 acts as an innate immune modulator by controlling antimicrobial responses in keratinocytes. J Invest Dermatol 2009; 129(9):2148"2155.
Li S, Huang M, Liu Q, Wang D, Wu R, Zhang X, Chen W, Duan L. Serum Expression of β-Catenin Is a Potential Detection Marker in Patients with Colorectal Cancer. Dis Markers 2019; 2019:5070524.
Obrocea FL, Sajin M, Marinescu EC, Stoica D. Colorectal cancer and the 7th revision of the TNM staging system: review of changes and suggestions for uniform pathologic reporting. Rom J Morphol Embryol 2011; 52(2):537"544.
Urban BC, Collard TJ, Eagle CJ, Southern SL, Greenhough A, Hamdollah-Zadeh M, Ghosh A, Poulsom R, Paraskeva C, Silver A, Williams AC. BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling. Gut 2016; 65(7):1151"1164.
Wulczyn FG, Naumann M, Scheidereit C. Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-kappa B. Nature 1992; 358(6387):597"599.
Valenta T, Hausmann G, Basler K. The many faces and functions of β"catenin EMBO J 2012; 31(12):2714"2736.
Hatipoglu OF, Yaykasli KO, Dogan M, Yaykasli E, Bender O, Yasar T, Tapan S, Gunduz M. NF-κB and MAPKs are involved in resistin caused ADAMTS-5 induction in Human Chondrocytes. Clin Invest Med 2015; 38(4): E248-E254.
Chen X, Wang C, Jiang Y, Wang Q, Tao Y, Zhang H, Zhao Y, Hu Y, Li C, Ye D, Liu D. Bcl-3 promotes Wnt signaling by maintaining the acetylation of β-catenin at lysine 49 in colorectal cancer. Signal Transduct Target Ther 2020; 5(1):52.
Narasipura SD, Henderson LJ, Fu SW, Chen L, Kashanchi F, Al-Harthi L. Role of β-catenin and TCF/LEF family members in transcriptional activity of HIV in astrocytes. J Virol 2012; 86(4):1911"1921.
Pećina-Å laus N, Kafka A, Lechpammer M. Molecular genetics of intracranial meningiomas with emphasis on canonical Wnt signalling. Cancers (Basel) 2016; 8(7):67.
Blum CA, Xu M, Orner GA, et al. 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 [published correction appears in Carcinogenesis 2001 Apr;22(4):685]. Carcinogenesis 2001; 22(2):315"320.
Nelson, R.L. Dietary minerals and colorectal cancer. In: Rowland, I.R. Nutrition, Toxicity and Cancer. CRC Press, London, pp: 1991; 491-515.
Yamak N, Yaykasli KO, Yilmaz U, Eroz R, Uzunlar AK, Ankaralı H, Sahiner C, Baltaci D. Association Between Survivin Gene Polymorphisms and the Susceptibility to Colon Cancer Development in Turkish Population, Asian Pac J Cancer Prev 2014; 15(20):8963-8967.
Puvvada SD, Funkhouser WK, Greene K, Deal A, Chu H, Baldwin AS, Tepper JE, O'Neil BH. NF-ć¸B and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer. Oncology 2010; 78(3-4):181"188.
Collins PE, Kiely PA, Carmody RJ. Inhibition of transcription by B cell Leukemia 3 (Bcl-3) protein requires interaction with nuclear factor κB (NF-κB) p50. J Biol Chem 2014; 289(10):7059"7067.
Brocke-Heidrich K, Ge B, Cvijic H. BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription. Oncogene 2006; 25(55):7297"7304.
Taheri Z, Asadzadeh Aghdaei H, Irani S, Modarressi MH, Noormohammadi Z. Clinical Correlation of miR-200c/141 Cluster DNA Methylation and miR-141 Expression with the Clinicopathological Features of Colorectal Primary Lesions/Tumors. Rep Biochem Mol Biol. 2019;8(3):208"215.
Rezaei FM, Hashemzadeh S, Gavgani RR, Feizi MH, Pouladi N, Kafil HS, Rostamizadeh L, Oskooei VK, Taheri M, Sakhinia E. Dysregulated KDR and FLT1 Gene Expression in Colorectal Cancer Patients. Rep Biochem Mol Biol. 2019;8(3):244"252.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.