Retinoic acid nuclear receptor β inhibits breast carcinoma anchorage independent growth

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Abstract
Retinoids modulate cellular proliferation and mediate gene function through a series of nuclear receptors. The retinoic acid nuclear receptor β (RARβ) plays an important role in the differentiation of a number of cell types. We now demonstrate that RARβ expresion is confined to normal mammary tissue and is not expressed in either immortalized normal or malignant cell lines. Treatment of RARβ‐transfected MDA‐MB‐231 cells with 1 μM all‐trans‐retinoic acid (RA) significantly inhibited monolayer growth of the cells which express recombinant RARβ. RARβ‐expressing MDA‐MB‐231 cells formed significantly smaller and fewer colonies soft agar than the mock‐transfected cells. Addition of 1 μM RA stimulated colony size and number in the RARβ‐transfected MDA‐MB‐231 cells. In contast to the RARβ‐expressing cells, colony formation by the RARβ‐expressing cells was similar to the mock‐transfected controls and the addition of 1 μM RA to the RARα‐transfected cells inhibited colony formation. While demonstrating decreased colony formation in agar, RARβ‐expressing MDA‐MB‐231 cells failed to exhibit decreased growth in SCID mice. Our results show that RARβ functions as a negative regulator of growth in breast epithelial cells. In addition, the growth of these cells is differentially regulated by RARα and RARβ which is most likely the result to the modulation of different genes. © 1995 Wiley‐Liss Inc.