This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kohlgraf, K. G. Articles by Hollingsworth, M. A. Search for Related Content PubMed PubMed Citation Articles by Kohlgraf, K. G. Articles by Hollingsworth, M. A.

Contribution of the MUC1 Tandem Repeat and Cytoplasmic Tail to Invasive and Metastatic Properties of a Pancreatic Cancer Cell Line¹

Eppley Institute for Research in Cancer and Allied Diseases, and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805 [K. G. K., A. J. G., M. H., M. D. B., S. K., D. L. K., T. C. C., M. A. H.], and Department of Preventive and Societal Medicine, Biostatistics Section, University of Nebraska Medical Center, Omaha, Nebraska 68191-4350 [J. L. M.]

MUC1 is a polymorphic, highly glycosylated, type I transmembrane protein expressed by ductal epithelial cells of many organs including pancreas, breast, gastrointestinal tract, and airway. MUC1 is overexpressed and differentially glycosylated by adenocarcinomas that arise in these organs, and is believed to contribute to invasive and metastatic potential by contributing to cell surface adhesion properties [via the tandem repeat (TR) domain] and through morphogenetic signal transduction [via the cytoplasmic tail (CT)]. The large extracellular TR of MUC1 consists of a heavily glycosylated, 20 amino acid sequence that shows allelic variation with respect to number of repeats. This portion of MUC1 may directly mediate adhesive or antiadhesive interactions with other surface molecules on adjacent cells and through these interactions initiate signal transduction pathways that are transmitted through the CT. We investigated the contribution of the TR domain and the CT of MUC1 to the in vivo invasive and metastatic potential, and the gene expression profile of the human pancreatic tumor cell line S2-013. Results showed that S2-013 cells overexpressing full-length MUC1 displayed a less invasive and metastatic phenotype compared with control-transfected cells and cells expressing MUC1 lacking the TR domain or CT. Clonal populations were analyzed by cDNA array gene expression analysis, which showed differences in the gene expression profiles between the different cell lines. Among the genes differentially expressed were several that encode proteins believed to play a role in invasion and metastasis.

This article has been cited by other articles:

				C. Patriarca, P. Colombo, A. Pio Taronna, J. Wesseling, G. Franchi, F. Guddo, R. Naspro, R. M. Macchi, P. Giunta, M. Di Pasquale, et al. Cell Discohesion and Multifocality of Carcinoma In situ of the Bladder: New Insight From the Adhesion Molecule Profile (e-Cadherin, Ep-CAM, and MUC1) International Journal of Surgical Pathology, April 1, 2009; 17(2): 99 - 106. [Abstract] [PDF]

				P. K. Singh, M. E. Behrens, J. P. Eggers, R. L. Cerny, J. M. Bailey, K. Shanmugam, S. J. Gendler, E. P. Bennett, and M. A. Hollingsworth Phosphorylation of MUC1 by Met Modulates Interaction with p53 and MMP1 Expression J. Biol. Chem., October 3, 2008; 283(40): 26985 - 26995. [Abstract] [Full Text] [PDF]

				T. L. Tinder, D. B. Subramani, G. D. Basu, J. M. Bradley, J. Schettini, A. Million, T. Skaar, and P. Mukherjee MUC1 Enhances Tumor Progression and Contributes Toward Immunosuppression in a Mouse Model of Spontaneous Pancreatic Adenocarcinoma J. Immunol., September 1, 2008; 181(5): 3116 - 3125. [Abstract] [Full Text] [PDF]

				M.-K. Shyu, M.-C. Lin, C.-H. Liu, Y.-R. Fu, J.-C. Shih, C.-N. Lee, H.-Y. Chen, J. Huang, M.-C. Huang, and F.-J. Hsieh MUC1 Expression Is Increased During Human Placental Development and Suppresses Trophoblast-Like Cell Invasion In Vitro Biol Reprod, August 1, 2008; 79(2): 233 - 239. [Abstract] [Full Text] [PDF]

				B. J. Swanson, K. M. McDermott, P. K. Singh, J. P. Eggers, P. R. Crocker, and M. A. Hollingsworth MUC1 Is a Counter-Receptor for Myelin-Associated Glycoprotein (Siglec-4a) and Their Interaction Contributes to Adhesion in Pancreatic Cancer Perineural Invasion Cancer Res., November 1, 2007; 67(21): 10222 - 10229. [Abstract] [Full Text] [PDF]

				M.-K. Shyu, M.-C. Lin, J.-C. Shih, C.-N. Lee, J. Huang, C.-H. Liao, I-F. Huang, H.-Y. Chen, M.-C. Huang, and F.-J. Hsieh Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro Hum. Reprod., October 1, 2007; 22(10): 2723 - 2732. [Abstract] [Full Text] [PDF]

				P. K. Singh, Y. Wen, B. J. Swanson, K. Shanmugam, A. Kazlauskas, R. L. Cerny, S. J. Gendler, and M. A. Hollingsworth Platelet-Derived Growth Factor Receptor {beta}-Mediated Phosphorylation of MUC1 Enhances Invasiveness in Pancreatic Adenocarcinoma Cells Cancer Res., June 1, 2007; 67(11): 5201 - 5210. [Abstract] [Full Text] [PDF]

				E. J. Thompson, K. Shanmugam, C. L. Hattrup, K. L. Kotlarczyk, A. Gutierrez, J. M. Bradley, P. Mukherjee, and S. J. Gendler Tyrosines in the MUC1 Cytoplasmic Tail Modulate Transcription via the Extracellular Signal-Regulated Kinase 1/2 and Nuclear Factor-{kappa}B Pathways Mol. Cancer Res., July 1, 2006; 4(7): 489 - 497. [Abstract] [Full Text] [PDF]

				H. Tsutsumida, B. J. Swanson, P. K. Singh, T. C. Caffrey, S. Kitajima, M. Goto, S. Yonezawa, and M. A. Hollingsworth RNA Interference Suppression of MUC1 Reduces the Growth Rate and Metastatic Phenotype of Human Pancreatic Cancer Cells. Clin. Cancer Res., May 15, 2006; 12(10): 2976 - 2987. [Abstract] [Full Text] [PDF]

				P. Baumann, N. Cremers, F. Kroese, G. Orend, R. Chiquet-Ehrismann, T. Uede, H. Yagita, and J. P. Sleeman CD24 Expression Causes the Acquisition of Multiple Cellular Properties Associated with Tumor Growth and Metastasis Cancer Res., December 1, 2005; 65(23): 10783 - 10793. [Abstract] [Full Text] [PDF]

				F. Santos-Silva, A. Fonseca, T. Caffrey, F. Carvalho, P. Mesquita, C. Reis, R. Almeida, L. David, and M. A. Hollingsworth Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism Glycobiology, May 1, 2005; 15(5): 511 - 517. [Abstract] [Full Text] [PDF]

				E. Gaudier, A. Jarry, H. M. Blottiere, P. de Coppet, M. P. Buisine, J. P. Aubert, C. Laboisse, C. Cherbut, and C. Hoebler Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1168 - G1174. [Abstract] [Full Text] [PDF]

				E Levi, D S Klimstra, N V Adsay, A Andea, and O Basturk MUC1 and MUC2 in pancreatic neoplasia J. Clin. Pathol., May 1, 2004; 57(5): 456 - 462. [Abstract] [Full Text] [PDF]

				Y. Wen, T. C. Caffrey, M. J. Wheelock, K. R. Johnson, and M. A. Hollingsworth Nuclear Association of the Cytoplasmic Tail of MUC1 and {beta}-Catenin J. Biol. Chem., September 26, 2003; 278(39): 38029 - 38039. [Abstract] [Full Text] [PDF]