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The Cellular Retinoic Acid Binding Protein II Is a Positive Regulator of Retinoic Acid Signaling in Breast Cancer Cells¹

Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029-6574

The role of the cellular retinoic acid binding protein type II (CRABPII) in the retinoic acid (RA) signaling pathway is poorly understood. Northern blot analysis of 12 breast cell lines showed that CRABPII mRNA content correlated with growth inhibition by RA, suggesting that this binding protein enhances cellular response to RA. Ectopic CRABPII expression supported dose-dependent growth inhibition by RA in SC115-resistant but not MDA-MB-231-resistant cells, indicating that CRABPII is sufficient to rescue RA antiproliferation in a permissive background. In both cell lines, ectopic binding protein enhanced gene activation by RA. Thus, induction of tissue transglutaminase by all-trans-RA and, surprisingly, 9-cis-RA was enhanced 5-fold over and above the level of induction in control cells (SC115), and activation of a RA response element reporter was enhanced 3-fold (MDA-MB-231). A 5-fold enhancement of RA induction of RA receptor ß expression as a result of ectopic binding protein expression was also demonstrated (SC115). These findings indicate that CRABPII is a positive regulator of RA signaling in breast cells.

¹ This work was supported by National Cancer Institute Grant CA54273 (to R. M-y-L.), The Samuel Waxman Foundation, The Chemotherapy Foundation, The Jaffe Family Foundation, and Hoffmann-La Roche.

² To whom requests for reprints should be addressed, at Department of Medicine, Box 1178, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574.

Received 12/18/96. Accepted 3/20/97.

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