DEXAMETHASONE INDUCES ALTERED BINDING OF REGULATORY FACTORS TO HLA CLASS-I ENHANCER SEQUENCE IN MCF-7 BREAST-TUMOR CELL-LINE

Several reports have shown the importance of MHC class I antigens in e nabling the host to regulate tumour growth in vivo, Glucocorticoid hor mones have strong immunosuppressive effects and are known regulators o f gene transcription. In this work we studied the expression of major histocompatibility complex (MHC) class I antigens in three breast carc inoma cell lines before and after treatment with the synthetic glucoco rticoid dexamethasone. HLA class I expression in the cell line MCF-7 w as downregulated in the presence of dexamethasone. This down modulatio n of expression appeared to be mediated by transcriptional mechanisms, as revealed by HLA class I mRNA levels. To elucidate the basis of MHC class I downregulation by dexamethasone, we examined transcriptional factor-binding activity to the HLA class I regulatory element or enhan cer A by electrophoretic-mobility-shift assays, using synthesized olig onucleotides corresponding to upstream conserved sequences of MHC clas s I genes. Our results showed that dexamethasone induced a different b inding to the MHC class I regulatory elements in the MCF-7 cell line f rom that of the other cell lines included in our study. MCF-7 cells pr esented a strong decrease in previous factor-binding activity to the C RE II probe (H2-RIIBP-like binding activity) and a new factor-binding activity was apparent. On the other hand, CRE I region showed an incre ase in KBF1-factor-binding activity. These results suggest that glucoc orticoids down-modulate the expression of MHC class I antigens by alte ring the binding to the enhancer A sequence. In addition, this down-mo dulation may affect the regulation of tumour growth by the host's immu ne system.