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

Abstract
The transcription factor retinoic acid receptor beta(2) (RARbeta(2)) is a potent inhibitor of breast cancer cells in vitro, and studies suggest that RARbeta expression is lost in primary breast cancer. Although RARbeta(2) is selectively down-regulated at the mRNA level in breast tumor cells, we show that expression of an RARbeta 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 RARbeta(4) transcript. Unlike the previously characterized mouse RARbeta(4) isoform, the human RARbeta(4) retains only half of a DNA-binding domain and lacks a ligand-independent transactivation domain at its N terminus. The RARbeta(4) protein localizes to the cytoplasm and to subnuclear compartments that resemble nuclear bodies. The structure and preliminary characterizations of human RARbeta(4), coupled with the observation that its expression is greatly elevated in breast tumor cell lines, support the hypothesis that RARbeta(4) functions as a dominant-negative repressor of RAR-mediated growth suppression.
AuthorsK M Sommer, L I Chen, P M Treuting, L T Smith, K Swisshelm
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 15 Pg. 8651-6 (Jul 20 1999) ISSN: 0027-8424 [Print] United States
PMID10411930 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • retinoic acid receptor beta
Topics
  • Base Sequence
  • Breast Neoplasms (metabolism)
  • Cell Nucleus (metabolism)
  • Cloning, Molecular
  • Cytoplasm (metabolism)
  • Gene Expression Regulation, Neoplastic (genetics)
  • Humans
  • Immunohistochemistry
  • Molecular Sequence Data
  • Neoplasm Proteins (genetics, metabolism)
  • Open Reading Frames
  • Protein Biosynthesis
  • RNA, Messenger (metabolism)
  • Receptors, Retinoic Acid (genetics, metabolism)
  • Repressor Proteins (genetics)
  • Tumor Cells, Cultured
  • Up-Regulation

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