Molecular cytogenetic characterization of two murine cancer cell lines derived from salivary gland

  • Ralf Steinacker Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1, D-07747 Jena, Germany
  • Thomas Liehr Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1, D-07747 Jena, Germany
  • Nadezda Kosyakova Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1, D-07747 Jena, Germany
  • Martina Rincic Department for Functional Genomics, Centre for Translational and Clinical Research, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
  • Shaymaa S. Hussein Azawi Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Am Klinikum 1, D-07747 Jena, Germany


Here two murine salivary gland cancer (SGC) cell lines WR21 and SCA-9 were studied for the first time in detail by high-resolution molecular cytogenetic approaches. This study revealed that these cell lines are models for human SGCs of initial stage myoepithelioid or mucoepidermoid (WR21) and of advanced stage mucoepidermoid (SCA-9) tumors. Besides, three genes most likely playing a role in SGC development (FGF10, ELAVL1/HUR and SEL1) were identified. All of them were involved in translocation events in these in vitro models and thus were most likely activated. Overall, the present study highlights the necessity not only to establish but also to genetically characterize murine tumor cell lines. Without such a characterization they cannot be used in a reasonable way in research.


salivary gland cancer (SGC), murine tumor cell lines, WR21, SCA-9, myoepithelioid SGC, mucoepidermoid SGC, FGF10, ELAVL1/HUR, SEL1


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Barrera, M. J., Aguilera, S., Castro, I., Cortés, J., Bahamondes, V., Quest, A. F. G., Molina, C., González, S., Hermoso, M., Urzúa, U., Leyton, C. and González, M. J. 2016. Pro-inflammatory cytokines enhance ERAD and ATF6α pathway activity in salivary glands of Sjögren’s syndrome patients. J Autoimmun 75(1):68–81.

Barka, T. 1980. Biologically active polypeptides in submandibular glands. J Histochem Cytochem 28(8):836–859.

Barka, T., Gresik, E. S. and Miyazaki, Y. 2005. Differentiation of a mouse submandibular gland-derived cell line (SCA) grown on matrigel. Exp Cell Res 308(2):394–406.

Cao, Y., Liu, H., Gao, L., Lu, L., Du, L., Bai, H., Li, J., Said, S., Wang, X., Song, J., Serkova, N., Wei, M., Xiao, J. and Lu, S. 2018. Cooperation between pten and smad4 in murine salivary gland tumor formation and progression. Neoplasia 20:764–774.

Cho, N. P., Han, H. S., Soh, Y. and Son, H. J. 2007. Overexpression of cyclooxygenase-2 correlates with cytoplasmic HuR expression in salivary mucoepidermoid carcinoma but not in pleomorphic adenoma. J Oral Pathol Med 36(5):297–203.

Davoli, T. and de Lange, T. 2012. Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cells. Cancer Cell 21(6):765–776.

El-Naggar, A. K., Dinh, M., Tucker, S. L., Gillenwater, A., Luna, M. A. and Batsakis, J. G. 1997. Chromosomal and DNA ploidy characterization of salivary gland neoplasms by combined FISH and flow cytometry. Hum Pathol 28(8):881–886.

Español, A., Dasso, M., Cella, M., Goren, N. and Sales, M. E. 2012. Muscarinic regulation of SCA-9 cell proliferation via nitric oxide synthases, arginases and cyclooxygenases. Role of the nuclear translocation factor-κB. Eur J Pharmacol 683(1–3):43–53.

Fowler, M. H., Fowler, J., Ducatman, B., Barnes, L. and Hunt, J. L. 2006. Malignant mixed tumors of the salivary gland: a study of loss of heterozygosity in tumor suppressor genes. Mod Pathol 19(3):350–355.

Guja, K., Liehr, T., Rincic, M., Kosyakova, N. and Hussein Azawi, S. S. 2017. Molecular cytogenetic characterization identified the murine B-cell lymphoma cell line A-20 as a model for sporadic Burkitt’s lymphoma. J Histochem Cytochem 65(11):669–677.

Hungermann, D., Roeser, K., Buerger, H., Jakel, T., Loening, T. and Herbst, H. 2002. Relative paucity of gross genetic alterations in myoepitheliomas and myoepithelial carcinomas of salivary glands. J Pathol 198(4):487–494.

Itoh, N. and Ohta, H. 2014. Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine. Curr Mol Med 14(4):504–509.

Jee, K. J., Persson, M., Heikinheimo, K., Passador-Santos, F., Aro, K., Knuutila, S., Odell, E. W., Mäkitie, A., Sundelin, K., Stenman, G. and Leivo, I. 2013. Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma. Mod Pathol 26(2):213–222.

Keller, G., Steinmann, D., Quaas, A., Grünwald, V., Janssen, S. and Hussein, K. 2017. New concepts of personalized therapy in salivary gland carcinomas. Oral Oncol 68(1):103–113.

Krejci, P., Prochazkova, J., Bryja, V., Kozubik, A. and Wilcox, W. R. 2009. Molecular pathology of the fibroblast growth factor family. Hum Mutat 30(9):1245–1255.

Kubicova, E., Trifonov, V., Borovecki, F., Liehr, T., Rincic, M., Kosyakova, N. and Hussein, S. S. 2017. First molecular cytogenetic characterization of murine malignant mesothelioma cell line AE17 and in silico translation to the human genome. Curr Bioinform 12(1):11–18.

Leibiger, C., Kosyakova, N., Mkrtchyan, H., Glei, M., Trifonov, V. and Liehr, T. 2013. First molecular cytogenetic high resolution characterization of the NIH 3T3 cell line by murine multicolor banding. J Histochem Cytochem 61(4):306–312.

Liehr, T., Starke, H., Heller, A., Kosyakova, N., Mrasek, K., Gross, M., Karst, C., Glaser, M., Fickelscher, I., Kuechler, A., Trifonov, V., Romanenko, S. A. and Weise, A. 2006. Multicolor fluorescence in situ hybridization (FISH) applied to FISH-banding. Cytogenet Genome Res 114(3–4):240–244.

Mastromonaco, G. F., Perrault, S. D., Betts, D. H. and King, W. A. 2006. Role of chromosome stability and telomere length in the production of viable cell lines for somatic cell nuclear transfer. BMC Dev Biol 6(1):41.

Martins, C., Fonseca, I., Felix, A., Roque, L. and Soares, J. 1995. Benign salivary gland tumors: A cytogenetic study of 21 cases. J Surg Oncol 60(4):232–237.

Matse J. H., Veerman E. C. I., Bolscher J. G. M., René Leemans C., Ylstra B. and Bloemena E. 2017. High number of chromosomal copy number aberrations inversely relates to t(11;19)(q21;p13) translocation status in mucoepidermoid carcinoma of the salivary glands. Oncotarget 8(41):69456–69464.

Murase, R., Sumida, T., Kawamura, R., Onishi-Ishikawa, A., Hamakawa, H., McAllister, S. D. and Desprez, P. 2016. Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression. Cancer Lett 377(1):11–16.

Müller, S. 2013. An update on salivary gland pathology. Head Neck Pathol 7 (Suppl 1):S1–S2.

Nielsen, L. L., Gurnani, M., Porter, G., Trexler, S., Emerson, D. and Tyler, R. D. 1994. Development of a nude mouse model of ras-mediated neoplasia using WR21 cells from a transgenic mouse salivary tumor. In Vivo 8(3):295–302.

Omitola, O. G. and Iyogun, C. A. 2018. Immunohistochemical study of salivary gland tumors in a tertiary institution in South-South Region of Nigeria. J Oral Maxillofac Pathol 22(2):163–167.

Palanisamy, V., Park, N. J., Wang, J. and Wong, D. T. 2008. AUF1 and HuR proteins stabilize interleukin-8 mRNA in human saliva. J Dent Res 87(8):772–776.

Persson, F., Andrén, Y., Winnes, M., Wedell, B., Nordkvist, A., Gudnadottir, G., Dahlenfors, R., Sjögren, H., Mark, J. and Stenman, G. 2009. High-resolution genomic profiling of adenomas and carcinomas of the salivary glands reveals amplification, rearrangement, and fusion of HMGA2. Genes Chromosomes Cancer 48(1):69–82.

Rao, P. H., Roberts, D., Zhao, Y., Bell, D., Harris, C. P., Weber, R. S. and El-Naggar, A. K. 2008. Deletion of 1p32-p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands. Clin Cancer Res 14(16):5181–5187.

Rhode, H., Liehr, T., Kosyakova, N., Rincic, M. and Azawi, S. S. H. 2018. Molecular cytogenetic characterization of two murine colorectal cancer cell lines. OBM Genetics 2(3).

Seethala, R. R. 2017. Salivary gland tumors: current concepts and controversies. Surg Pathol Clin 10(1):155–176.

Solanki, G. 2011. Tumors of salivary glands. IJPR 1(2):35–38.

Sood, S., McGurk, M. and Vaz, F. 2016. Management of salivary gland tumours: United Kingdom national multidisciplinary guidelines. J Laryngol Otol 130(S2):S142–S149.

Trzaskawka, E., Vigo, J., Egea, J.-C., Goldsmith, M.-C., Salmon, J.-M., Deville and De Periere, D. 2000. Cultured tumor cells of murine submandibular gland origin: a model to investigate pHi regulation of salivary cells. Eur J Oral Sci 108(1):54–58.

Vekony, H., Röser, K., Löning, T., Ylstra, B., Meijer, G. A., van Wieringen, W. N., van de Wiel, M. A., Carvalho, B., Kok, K., Leemans, S. R., van der Waal, I. and Bloemena, E. 2009. Copy number gain at 8q12.1-q22.1 is associated with a malignant tumor phenotype in salivary gland myoepitheliomas. Genes Chromosomes Cancer 48(2):202–212.

Yin, L. X. and Ha, P. K. 2016. Genetic alterations in salivary gland cancers. Cancer 122(12):1822–1831.

Young, L. F. and Martin, K. R. 2006. Time-dependent resveratrol-mediated mRNA and protein expression associated with cell cycle in WR-21 cells containing mutated human c-Ha-Ras. Mol Nutr Food Res 50(1):70–77.

Zboray, K., Mohrherr, J., Stiedl, P., Pranz, K., Wandruszka, L., Grabner, B., Eferl, R., Moriggl, R., Stoiber, D., Sakamoto, K., Wagner, K., Popper, H., Casanova, E. and Moll, H. 2018. AKT3 drives adenoid cystic carcinoma development in salivary glands. Cancer Med 7(2):445–453.

How to Cite
Steinacker, R., Liehr, T., Kosyakova, N., Rincic, M., & Hussein Azawi, S. (2019). Molecular cytogenetic characterization of two murine cancer cell lines derived from salivary gland. Biological Communications, 63(4), 243–255.
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