期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1999
卷号:96
期号:15
页码:8651-8656
DOI:10.1073/pnas.96.15.8651
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:The transcription factor retinoic acid receptor {beta}2 (RAR{beta}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}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}4 transcript. Unlike the previously characterized mouse RAR{beta}4 isoform, the human RAR{beta}4 retains only half of a DNA-binding domain and lacks a ligand-independent transactivation domain at its N terminus. The RAR{beta}4 protein localizes to the cytoplasm and to subnuclear compartments that resemble nuclear bodies. The structure and preliminary characterizations of human RAR{beta}4, coupled with the observation that its expression is greatly elevated in breast tumor cell lines, support the hypothesis that RAR{beta}4 functions as a dominant-negative repressor of RAR-mediated growth suppression.