This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Meuillet, E. J. Articles by Bremer, E. G. Search for Related Content PubMed PubMed Citation Articles by Meuillet, E. J. Articles by Bremer, E. G.

Sialidase Gene Transfection Enhances Epidermal Growth Factor Receptor Activity in an Epidermoid Carcinoma Cell Line, A431¹

The Brain Tumor Research Program, Children’s Memorial Hospital and The Chicago Institute for Neurosurgery and Neuroresearch, Chicago, Illinois 60614 [E. J. M., R. K., H. Y., B. M-F., D. G., H. R., J. R. M., E. G. B.], and Genentech, Inc., South San Francisco, California 94080 [T. G. W., J. F.]

Glycosphingolipids expressed in cancer cells have been implicated in the modulation of tumor cell growth through their interaction with transmembrane signaling molecules such as growth factor receptors. For glycosphingolipids to interact with growth factor receptors, the presence of sialic acid seems to be essential. Stable transfection of a gene encoding a soluble M_r 42,000 sialidase into a human epidermoid carcinoma cell line (A431) provided an approach by which the level of terminal lipid-bound sialic acid on the cell surface could be altered. In the sialidase-positive clones, the level of ganglioside GM3 was diminished, and little change was observed in protein sialylation. Sialidase-transfected cells grew faster than control cells. Sialidase expression did not modify the binding of epidermal growth factor (EGF) to its receptor but enhanced EGF receptor (EGFR) tyrosine autophosphorylation as compared to that of parental cells or cells transfected with the vector (pcDNA3) alone. Moreover, the phosphorylation of the EGFR, as well as other protein substrates, was observed at low EGF concentrations, suggesting an increase in the receptor kinase sensitivity. These data provided evidence that changes in ganglioside expression in cancer cells by appropriate gene transfection can dramatically affect EGFR kinase activity. Hence, the modulation of ganglioside expression may represent an approach to alter tumor cell growth.

This article has been cited by other articles:

				H.-J. Choi, T.-W. Chung, S.-J. Kim, S.-Y. Cho, Y.-S. Lee, Y.-C. Lee, J.-H. Ko, and C.-H. Kim The AP-2{alpha} transcription factor is required for the ganglioside GM3-stimulated transcriptional regulation of a PTEN gene Glycobiology, May 1, 2008; 18(5): 395 - 407. [Abstract] [Full Text] [PDF]

				E. Masson, L. Troncy, D. Ruggiero, N. Wiernsperger, M. Lagarde, and S. E. Bawab a-Series Gangliosides Mediate the Effects of Advanced Glycation End Products on Pericyte and Mesangial Cell Proliferation: A Common Mediator for Retinal and Renal Microangiopathy? Diabetes, January 1, 2005; 54(1): 220 - 227. [Abstract] [Full Text] [PDF]

				C. Tringali, N. Papini, P. Fusi, G. Croci, G. Borsani, A. Preti, P. Tortora, G. Tettamanti, B. Venerando, and E. Monti Properties of Recombinant Human Cytosolic Sialidase HsNEU2: THE ENZYME HYDROLYZES MONOMERICALLY DISPERSED GM1 GANGLIOSIDE MOLECULES J. Biol. Chem., January 30, 2004; 279(5): 3169 - 3179. [Abstract] [Full Text] [PDF]

				S. Y. Boateng, T. J. Hartman, N. Ahluwalia, H. Vidula, T. A. Desai, and B. Russell Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography Am J Physiol Cell Physiol, July 1, 2003; 285(1): C171 - C182. [Abstract] [Full Text] [PDF]

				E. A. Miljan and E. G. Bremer Regulation of Growth Factor Receptors by Gangliosides Sci. Signal., November 26, 2002; 2002(160): re15 - re15. [Abstract] [Full Text] [PDF]

				P. M. Crespo, A. R. Zurita, and J. L. Daniotti Effect of Gangliosides on the Distribution of a Glycosylphosphatidylinositol-anchored Protein in Plasma Membrane from Chinese Hamster Ovary-K1 Cells J. Biol. Chem., November 15, 2002; 277(47): 44731 - 44739. [Abstract] [Full Text] [PDF]

				F. Alves, U. Borchers, H. Keim, R. Fortte, J. Olschimke, W. F. Vogel, H. Halfter, and L. F. Tietze Inhibition of EGF-mediated receptor activity and cell proliferation by HK1-ceramide, a stable analog of the ganglioside GM3-lactone Glycobiology, August 1, 2002; 12(8): 517 - 522. [Abstract] [Full Text] [PDF]

				T. Ringerike, F. D. Blystad, F. O. Levy, I. H. Madshus, and E. Stang Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae J. Cell Sci., March 15, 2002; 115(6): 1331 - 1340. [Abstract] [Full Text] [PDF]

				E. A. Miljan, E. J. Meuillet, B. Mania-Farnell, D. George, H. Yamamoto, H.-G. Simon, and E. G. Bremer Interaction of the Extracellular Domain of the Epidermal Growth Factor Receptor with Gangliosides J. Biol. Chem., March 15, 2002; 277(12): 10108 - 10113. [Abstract] [Full Text] [PDF]

				R. Li, Y. Liu, and S. Ladisch Enhancement of Epidermal Growth Factor Signaling and Activation of Src Kinase by Gangliosides J. Biol. Chem., November 9, 2001; 276(46): 42782 - 42792. [Abstract] [Full Text] [PDF]

				X.-Q. Wang, P. Sun, M. O'Gorman, T. Tai, and A. S. Paller Epidermal growth factor receptor glycosylation is required for ganglioside GM3 binding and GM3-mediated suppresion of activation Glycobiology, July 1, 2001; 11(7): 515 - 522. [Abstract] [Full Text] [PDF]

				H. Takematsu, S. Diaz, A. Stoddart, Y. Zhang, and A. Varki Lysosomal and Cytosolic Sialic Acid 9-O-Acetylesterase Activities Can Be Encoded by One Gene via Differential Usage of a Signal Peptide-encoding Exon at the N Terminus J. Biol. Chem., September 3, 1999; 274(36): 25623 - 25631. [Abstract] [Full Text] [PDF]

				R. Li, J. Manela, Y. Kong, and S. Ladisch Cellular Gangliosides Promote Growth Factor-induced Proliferation of Fibroblasts J. Biol. Chem., October 27, 2000; 275(44): 34213 - 34223. [Abstract] [Full Text] [PDF]