Modulation of EGF receptor activity by changes in the GM3 content in a human epidermoid carcinoma cell line, A431

Emmanuelle Meuillet, Barbara Mania-Farnell, David George, Jin Ichi Inokuchi, Eric G. Bremer

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Gangliosides have been described as modulators of growth factor receptors. For example, GM3 addition in cell culture medium inhibits epidermal growth factor (EGF)-stimulated receptor autophosphorylation. Furthermore, depletion of ganglioside by sialidase gene transfection appeared to increase EGF receptor (EGFR) autophosphorylation. These data suggested that changes in GM3 content may result in different responses to EGF. In this study, the ceramide analog D-threo-1-phenyl-2-decannoylamino-3-morpholino-1- propanol ([D]-PDMP), which inhibits UDP-glucoseceramide glucosyltransferase, and addition of GM3 to the culture medium were used to study the effects of GM3 on the EGFR. Addition of 10 μM [D]-PDMP to A431 cells resulted in significant GM3 depletion. Additionally, EGFR autophosphorylation was increased after EGF stimulation. When exogenous GM3 was added in combination with [D]-PDMP, the enhanced EGFR autophosphorylation was returned to control levels. [D]-PDMP also increased EGF-induced cell proliferation, consistent with its effect on autophosphorylation. Once again, the addition of GM3 in combination with [D]-PDMP reversed these effects. These results indicate that growth factor receptor functions can be modulated by the level of ganglioside expression in cell lines. Addition of GM3 inhibits EGFR activity and decrease of GM3 levels using [D]-PDMP treatment enhances EGFR activity. Modulation of growth factor receptor function may provide an explanation for how transformation-dependent ganglioside changes contribute to the transformed phenotype. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalExperimental Cell Research
Volume256
Issue number1
DOIs
StatePublished - Apr 10 2000
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Squamous Cell Carcinoma
Gangliosides
Cell Line
Growth Factor Receptors
Epidermal Growth Factor
Culture Media
Glucosyltransferases
1-Propanol
Morpholinos
Uridine Diphosphate
Ceramides
Neuraminidase
Transfection
Cell Culture Techniques
Cell Proliferation
RV 538
Phenotype
Genes

Keywords

  • [D]-PDMP
  • Cancer
  • EGF receptor
  • Ganglioside
  • Proliferation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cell Biology

Cite this

Modulation of EGF receptor activity by changes in the GM3 content in a human epidermoid carcinoma cell line, A431. / Meuillet, Emmanuelle; Mania-Farnell, Barbara; George, David; Inokuchi, Jin Ichi; Bremer, Eric G.

In: Experimental Cell Research, Vol. 256, No. 1, 10.04.2000, p. 74-82.

Research output: Contribution to journalArticle

Meuillet, Emmanuelle ; Mania-Farnell, Barbara ; George, David ; Inokuchi, Jin Ichi ; Bremer, Eric G. / Modulation of EGF receptor activity by changes in the GM3 content in a human epidermoid carcinoma cell line, A431. In: Experimental Cell Research. 2000 ; Vol. 256, No. 1. pp. 74-82.
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