Non-Coding CK19 RNA in Peripheral Blood and Tissue of Breast Cancer Patients
Abstract
Breast carcinoma is the major cause of cancer-related death in women. The incidence of this carcinoma is rising and there are many attempts to decrease this problem. The aim of this study was detection of full-length cytokeratin 19 (CK19) mRNA, in peripheral blood and tissue of breast cancer patients in early stage of cancer. In this study, RT-PCR (reverse transcriptase-polymerase chain reaction) technique was used for detection of CK19 mRNA in peripheral blood and tissue of breast cancer patients. Primers were established to amplify the CK19 as a tumor marker. Moreover, CYFRA 21-1 subunit of CK19 protein was measured in the serum of patients. CK19 mRNA was detected and sequenced. It is shown that the most released CK19 mRNAs in blood and tissue of cancer patients are non-coding RNA. The mutated forms of mRNA are the incomplete transcripts of protein-coding gene as a long non-coding RNA (lncRNA) that could regulate gene expression. Moreover, small non-coding RNA (ncRNA) as fragments of CK19 is mostly observed in this experiment. They may play a role in tumorogenesis and their biologic exact function in breast cancer should be further elucidated.
Yang XR, Xu Y, Shi GM, Fan J, Zhou J, Ji Y, Sun HC, Qiu SJ, Yu B, Gao Q, He YZ, Qin WZ, Chen RX, Yang GH, Wu B, Lu Q, Wu ZQ, Tang ZY. Cytokeratin 10 and cytokeratin 19: Predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res 2008;14(12):3850-9.
Molloy TJ, Devriese LA, Helgason HH, Bosma AJ, Hauptmann M, Voest EE, Schellens JH, van't Veer LJ. A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer. Br J Cancer 2011;104(12):1913-9.
Möbus VJ, Moll R, Gerharz CD, Kieback DG, Merk O, Runnebaum IB, Linner S, Dreher L, Grill HJ, Kreienberg R. Differential characteristics of two newtumorigenic cell lines of human breast carcinoma origin. Int J Can 1998;77(3):415-23.
Bosma AJ, Weigelt B, Lambrechts AC, Verhagen OJ, Pruntel R, Hart AA, Rodenhuis S, van 't Veer LJ. Detection of circulating breast tumor cells by differential expression of marker genes. Clin Cancer Res 2002;8(6):1871-77.
Panteleakou Z, Lembessis P, Sourla A, Pissimissis N,Polyzos A, Deliveliotis C, Koutsilieris M. Detection of circulating tumor cells in prostate cancer patients:methodological pitfalls and clinical relevance. Mol Med 2009;15(3-4):101-14.
Keyhani M, Nasizadeh S, Dehghannejad A. Serum Ca15-3 Measurement in breast cancer patients before and after mastectomy. Arch Iran Med 2005;8(4):263-6.
Schrohl AS, Holten-Andersen M, Sweep F, Schmitt M, Harbeck N, Foekens J, Brünner N. European Organisation for Research and Treatment of Cancer (EORTC) Receptor and Biomarker Group. Tumor markers from laboratory to clinical utility. Mol Cell Proteomics2003;2(6):378-87.
Sharma S. Tumor markers in clinical practice: General principles and guidlines. Indian J Med Paediatr Oncol 2009;30(1):1-8.
Eltahir EM, Mallinson DS, Birnie GD, Hagan C, George WD, Purushotham AD. Putative markers for the detectionof breast carcinoma cells in blood. Br J Cancer 1998;77(8):1203-7.
Prasad S, Thraves P, Dritschilo A, Kuettel M. Expression Of cytokeratin-19 as a marker of neoplastic progression of human prostate epithelial cells. Prostate 1998;35(3):203-11.
Sarwar M, Tomiyoshi K, Inoue T, Fukazawa K, Endo K. Cyfra 21-1 as a tumor marker used in measuring the serum fragment of cytokeratin subunit 19 by immunoradiometricassay. Ann Nucl Med 1994;8(4):301-6.
Alix-Panabières C, Vendrell JP, Slijper M, Pellé O,Barbotte E, Mercier G, Jacot W, Fabbro M, Pantel K. Full- Length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer. Breast Cancer Res Treat 2009;11(3):1-10
Manhani AR, Manhani R, Soares HP, Bendit I, Lopes F, Nicoletti AG, Fonseca FL, Novaes M, Zatta SM, Arias V, Giralt S, del Giglio A. Ck-19 expression by RT-PCR in the peripheral blood of breast cancer patients correlates with response to chemotherapy. Breast Cancer Res Treat 2001;66(3):249-54.
Jiang WG, Martin TA, Mansel RE. Molecular detection of micro-metastasis in breast cancer. Crit Rev Oncol Hematol 2002;43(1):13-31.
Chen Y, Zou TN, Wu ZP, Zhou YC, Gu YL, Liu X, Jin CG, Wang XC. Detection of cytokeratin 19, human mammaglobin, and carcinoembryonic antigen-positivecirculating tumor cells by three-marker reverse transcription-PCR assay and its relation to clinical outcome in early breast cancer. Int J Biol Markers 2010;25(2):59-68.
Kahn HJ, Yang LY, Blondal J, Lickley L, Holloway C, Hanna W, Narod S, McCready DR, Seth A, Marks A. RTPCR amplification of CK19 mRNA in the blood ofbreast cancer patients: Correlation with established prognostic parameters. Breast Cancer Res Treat 2000;60(2):143-51.
Fujita J, Dohmoto K, Hojo S, Ueda Y, Bandoh S, Yang Y, Yamaji Y, Ohtsuki Y, Ishida T. The point mutation in the promoter region and the single nucleotide polymorphism in exon 1 of the cytokeratin 19 gene in human lung cancer cell lines. Lung Cancer 2001;34(3):387-94.
Dohmoto K, Hojo S, Fujita J, Yang Y, Ueda Y, Bandoh S, Yamaji Y, Ohtsuki Y, Dobashi N, Ishida T, Takahara J. The role of caspase 3 in producing cytokeratin 19 fragment (Cyfra21-1) in human lung cancer cell lines. Int J Cancer 2001;91(4):468-73.
Giovanella L, Ceriani L, Giardina G, Bardelli D, Tanzi F, Garancini S. Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: Comparison withcarbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA). Clin Chem Lab Med 2002;40(3):298-303.
Marrakchi R, Ouerhani S, Benammar S, Rouissi K,= Bouhaha R, Bougatef K, Messai Y, Khadimallah I, Rahal K, Ben Ammar-Elgaaied A. Detection of cytokeratin 19 mRNA and CYFRA 21-1 (cytokeratin 19 fragments) in blood of Tunisian women with breast cancer. Int J Biol Markers 2008;23(4):238-43.
Kordek R, Potemski P, Kusinska R, Pluciennik E, Bednarek A. Basal keratin expression in breast cancer byquantification of mRNA and by immunohistochemistry. J Exp Clni Cancer Res 2010;28;29:39.
Ueda Y, Fujita J, Bandoh S, Hojo S, Yamaji Y, Ohtsuk Y, Dobashi N, Takahara J. Expression of cytokeratin 19 mRNA in human lung cancer cell lines. Int J Cancer 1999;81(6):939-43.
Ruud P, Fodstad O , Hovig E. Identification of a novel cytokeratin 19 pseudogene that may interfere with reverse transcriptase-polymerase chain reaction assays used to detect micrometastatic tumor cells. Int J Cancer 1999;80(1):119-25.
Trummer A, Kadar J, Arseniev L, Petersen D,Lichtinghagen R, Ganser A. Competitive cytokeratin 19 RT-PCR for quantification of breast cancer cells in blood cell suspensions. J Hematother Stem Cell Res 2000; 9(2):275-84.
Pink RC, Wicks K, Caley DP, Punch EK, Jacobs L, Carter DR. Pseudogenes: Pseudo-Functional or Key Regulators in Health and Disease? RNA 2011;17(5):792-8.
Frowein JV, Pagel P, Kappler R, Schweinitz DV, Roscher A. Schmid I. MicroRNA-492 is processed from the keratin
gene and up-regulated in metastatic hepatoblastoma. Hepatology 2011;53(3):833-42.
Friel AM, Corcoran C, Crown J, O'Driscoll L. Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer. Breast Cancer Res Treat. 2010; 123(3):613-25.
Alix-Panabières C, Vendrell JP, Pellé O, Rebillard X, Riethdorf S, Müller V, Fabbro M, Pantel K. Detection and characterization of putative metastatic precursor cells in cancer patients. Clin Chem 2007;53(3):537-8.
Li WL, Su J, Yao YC, Tao XR, Yan YB, Yu HY, Wang XM, Li JX, Yang YJ, Lau JT, Hu YP. Isolation and characterization of bipotent liver progenitor cells from adult mouse. Stem Cells 2006;24(2):322-32.
Tzur G, Levy A, Meiri E, Barad O, Spector Y, Bentwich Z, Mizrahi L, Katzenellenbogen M, Ben-Shushan E, Reubinoff BE, Galun E. MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells. PLoS one 2008;3(11):e3726.
Harrison PM, Zheng D, Zhang Z, Carriero N, Gerstein M. Transcribed processed pseudogenes in the human genome: an intermediate form of expressed retrosequence lacking protein-coding ability. Nucleic Acids Res 2005; 33(8):2374-83.
Files | ||
Issue | Vol 51, No 2 (2013) | |
Section | Original Article(s) | |
Keywords | ||
Breast cancer CK19 Non-Coding RNA Tumor marker |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |