Gangliosides in regulation of ErB-2 and EGFR expression and activation

EGFR and ErbB2 are two type I transmembrane tyrosine-kinase receptors. They belong to the ErbB super-family whose members are engaged in extensive network of homo- and hetero-associations resulting in signal diversification and multiple cellular responses; the relative expression levels of the various receptors and the concentration of their respective ligands determine the composition of homo- and heterodimers. Our attention focused on the ligand orphan ErbB2 tyrosine-kinase that plays an important role in growth and differentiation of the mammary gland; moreover, its amplification and over-expression is found in many kind of tumours and represents a main feature for a pour prognosis of breast cancer. ErbB2 is the preferred heterodimerization partner of all the other ErbB proteins, included EGFR, and enhances ligand binding affinity and signalling power due to its potent latent kinase activity. To investigate the functional influence and molecular interactions between gangliosides, EGFR and ErbB2, we used the mouse mammary epithelial HC11 cell line, a suitable experimental model as it physiologically expresses ErbB2 in a manner dependent on the degree of cell confluence in culture and the stimulation with EGF. To point up even more clearly the association between EGFR, ErbB2 and gangliosides at the molecular level, the EGFR and ErbB2 expression and activation have been analysed in normal and ganglioside-depleted HC11 cells.