PERTURBING CELL-SURFACE BETA-(1,4)-GALACTOSYLTRANSFERASE ON F9 EMBRYONAL CARCINOMA-CELLS ARRESTS CELL-GROWTH AND INDUCES LAMININ SYNTHESIS

Cell growth and differentiation are influenced by intercellular contac t, suggesting that cell adhesion molecules may be instrumental in trig gering these events. F9 embryonal carcinoma cells are an ideal system in which to examine the function of cell adhesion molecules in growth and differentiation, since the relevant cell adhesion molecules and di fferentiation markers are well defined. Intercellular adhesion in F9 c ells is mediated by uvomorulin, or E-cadherin, and cell surface beta-( 1,4)-galactosyltransferase. Since previous studies suggested that neit her F9 cell growth nor differentiation is directly dependent on uvomor ulin function, in this study we examined whether cell surface galactos yltransferase plays any role in F9 cell growth or differentiation. A v ariety of galactosyltransferase perturbants, including anti-galactosyl transferase antibodies, UDPgalactose, and the substrate modifier prote in alpha-lactalbumin, inhibited the growth of F9 cells, whereas contro l reagents did not. To examine this in more detail, we analyzed the ef fects of perturbing surface galactosyltransferase on progression throu gh the F9 cell cycle. Anti-galactosyltransferase IgG treatment inhibit ed ornithine decarboxylase activity and lengthened the F9 cell cycle d uring G(1) and G(2), the latter mimicking the effects of retinoic acid , a reagent known to prolong the F9 cell cycle and induce differentiat ion. In contrast, anti-uvomorulin antibodies had no effect on F9 cell growth, ornithine decarboxylase activity, or progression through the c ell cycle. Furthermore, perturbation of surface galactosyltransferase adhesions in F9 cell aggregates induced precocious F9 cell differentia tion, as assayed by increased laminin synthesis, whereas control reage nts had no effect. Thus, perturbing surface galactosyltransferase adhe sions in F9 cells both decreases growth and stimulates synthesis of la minin. These results imply that interactions between surface galactosy ltransferase and its oligosaccharide ligand during cell adhesion may a ffect the normal growth-regulatory and differentiation-inducing signal s, as is seen, in part, during treatment with retinoic acid.