UPMODULATION BY ESTROGEN OF HLA CLASS-I EXPRESSION IS BREAST-TUMOR CELL-LINES

The expression of major histocompatibility complex (MHC) class I antigens was studied in five breast carcinoma cell lines before and after treatment with 17-beta estradiol. Increased HLA class I antigen expression correlated with the presence of estrogen receptors. The modulation of expression appeared to be mediated by transcriptional mechanisms, as revealed by class I mRNA levels. To elucidate the basis of MHC class I upregulation, we examined transcriptional factor binding activity to the class I regulatory element (CRE). Our results showed that 17-beta estradiol induced increases in factor binding activity to the CRE II probe, and decreases to the CRE I probe. In addition, our results suggested that factors that bind the CRE I region may modulate the binding of CRE II. Binding to CRE II was significantly increased in extracts pretreated with a competitor that contained the CRE I sequence, and that bound NF-kB/kBF1. In addition, induction of NF-kB binding activity by the tumor necrosis factor was accompanied by a decrease in nuclear factors that bind to the CRE II region.