Modulation of MHC gene expression in human breast carcinoma cells by hormones

Abstract

Products encoded by the class I Major Histocompatibility Complex (MHC) genes serve as restriction molecules which enable T cells to generate an immune response to specific antigens. Recently, many investigators have demonstrated the importance of class I antigens in enabling the host to regulate tumor growth in vivo. In this report, we have studied the regulation of HLA genes by hormones in human breast cancer cell lines. Eight lines were studied. Using HLA locus-specific DNA probes, the levels of HLA-A and HLA-B specific mRNAs were found to be underrepresented in six of these cell lines when compared to an epithelial cell line derived from a normal lactating breast. Moreover, the expression of class I MHC mRNA in these cells correlated well with the level of chloramphenicol acetyltransferase (CAT) activity detected after the introduction of exogenous HLA-CAT DNA-constructs. It was also found that HLA expression in some of the breast carcinoma cell lines could be modulated by the addition of hormones. Hence, HLA mRNA expression in the cell line MCF-7 was enhanced by the addition of estrogen; but was down-regulated in the presence of dexamethasone. Conversely, for T-47D cells, HLA expression was suppressed by progesterone. These results indicate that hormones could have an influence on the expression of HLA genes and may therefore indirectly be involved in the regulation of tumor growth by the host's immune system.