RETINOBLASTOMA PROTEIN-REGULATION OF SURFACE CD74 (INVARIANT CHAIN) EXPRESSION IN BREAST-CARCINOMA CELLS

The HLA class II genes encode heterodimeric cell surface proteins whic h bind peptide antigen recognized by T-cell receptors on CD4+ T-cells. The class II proteins are inducible by IFN-gamma, and this induction requires, or is strongly enhanced, by retinoblastoma protein (RB) in a series of breast carcinoma cell lines. Loading of peptide onto the cl ass II protein appears to be regulated by CD74, which associates with class II during their transition to the endosomal compartment, where c lass II binds peptide. Class II proteins and CD74 are largely regulate d in concert, provoking the question, is CD74 induction by IFN-gamma a ffected by RE? Results described here indicate that IFN-gamma inductio n of CD74 surface expression in a series of breast carcinoma lines is enhanced by RE, while RE has no effect on CD74 mRNA induction. Also, n either the class II nor the CD74 promoter regions are activated by RE in cotransfection experiments where RE activates the SV40 promoter.