Elevated retinoic acid receptor beta sub(4) protein in human breast tumor cells with nuclear and cytoplasmic localization

The transcription factor retinoic acid receptor beta sub(2) (RAR beta sub(2)) is a potent inhibitor of breast cancer cells in vitro, and studies suggest that RAR beta expression is lost in primary breast cancer. Although RAR beta sub(2) is selectively down-regulated at the mRNA level in breast tumor cells, we show that expression of an RAR beta protein is elevated in five of five breast tumor cell lines relative to normal human mammary epithelial cells. Subsequent analysis identified this protein as the translation product of the human RAR beta sub(4) transcript. Unlike the previously characterized mouse RAR beta sub(4) isoform, the human RAR beta sub(4) retains only half of a DNA- binding domain and lacks a ligand-independent transactivation domain at its N terminus. The RAR beta sub(4) protein localizes to the cytoplasm and to subnuclear compartments that resemble nuclear bodies. The structure and preliminary characterizations of human RAR beta sub(4), coupled with the observation that its expression is greatly elevated in breast tumor cell lines, support the hypothesis that RAR beta sub(4) functions as a dominant-negative repressor of RAR- mediated growth suppression.