Repression ofTransactivation of the Retinoic Acid Receptor β2 Promoter in Human Breast Cancer Cells

Abstract In previous studies, we have shown that the expression of retinoic acid receptor β2 (RARβ2) is altered in certain breast cancer cell lines. To investigate the mechanism responsible for this change, we studied in detail the RARβ2 promoter in cell lines which demonstrated altered expression and compared these results to cell lines in which RARβ2 was expressed normally. Direct DNA sequencing failed to identify alterations in the sequences of the known response elements in the cell lines manifesting altered expression patterns. By contrast, electrophoretic mobility shift studies of the proteins binding to these response elements demonstrated striking differences in the cells in which expression was altered, when compared to patterns seen in normal cells. Moreover, transient transfection studies using constructs of the RARβ2 promoter demonstrated an absence of trans activation in the lines in which the expression of this gene was altered. These data suggest that the mechanism responsible for loss of induction of RARβ2 in breast tumor cells is, at least in part, transcriptional repression.