Suppression by retinoic acid of epidermal growth factor receptor autophosphorylation and glycosylation in cultured human head and neck squamous carcinoma cells.

The epidermal growth factor receptor (EGF-R) gene is overexpressed or amplified in various human squamous cell carcinomas, including those of the head and neck (HNSCC). Earlier we found that beta-all-trans-retinoic acid (RA) inhibited the growth and suppressed the aberrant squamous cell differentiation of several cultured HNSCC cell lines. Here we examined the effects of RA on the expression and function of EGF-R in two HNSCC cell lines, 1483 and 183, which exhibit distinct states of squamous cell differentiation, EGF-R mRNA levels, and responses to the growth inhibitory effects of RA. Treatment with RA (1 microM, 7 days) of the RA-sensitive 1483 cells decreased the level of EGF-R mRNA two- to four-fold and the binding of 125I-EGF to the cell surface by 30%-35%. In contrast, RA treatment of the 183 cells did not alter the EGF-R mRNA level or the binding of 125I-EGF. Other effects of RA on EGF-R structure and function were similar in both cell lines. RA did not alter the amount of immunoprecipitable [35S]methionine-labeled cellular EGF-R, 125I-cell surface labeled EGF-R, EGF-R internalization, or transforming growth factor alpha (TGF-alpha) mRNA. More important, RA treatment of both cell lines decreased EGF-R autophosphorylation activity detected in immune-complex-kinase assay by about three- and five-fold in the 1483 and 183 cells, respectively. Likewise, RA decreased the glycosylation of EGF-R in both cell lines. In the 1483 cells, RA suppressed the incorporation of either glucosamine or fucose by about 50%, whereas in the 183 cells RA suppressed the incorporation of fucose by about 80%. These results demonstrate that RA can modify the structure of the EGF-R by decreasing its glycosylation and suggest that these changes may suppress the autophosphorylation activity of the receptor kinase. The RA-induced changes in EGF-R do not correlate with the effect of RA on the growth of the cells but may be related to the suppression of squamous cell differentiation in the 1483 cells.