1. ¹Department of Surgical Oncology, University of Illinois at Chicago, 840 South Wood Street, M/C 820, Chicago, IL 60612, USA
2. ²Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA

Correspondence: K Christov, E-mail: christov@uic.edu

³Current address: IIT Research Institute, 10 West 35th Street, Chicago IL 60616, USA.

Received 7 June 2004; Revised 4 October 2004; Accepted 4 October 2004; Published online 22 November 2004.

Abstract

Functional significance of RAR2 as a putative tumor suppressor gene has been studied in breast cancer and other tumors. The long 5'-untranslated region (5'-UTR) of its transcript with multiple open-reading frames (uORFs) is considered as a regulatory unit for translation. Here, for the first time we identified RAR2 transcript variants with short 5'-UTRs in both normal and malignant breast epithelial cells. The 5'-RACE analysis of RAR2 mRNA in these cells demonstrated the existence of short RAR2 transcript variants that are identical to the sequence of known RAR2, but lack all the uORFs present in the full-length 5'-UTR. By RT–PCR analysis, we found that the expression of both transcripts with short and full-length 5'-UTR is mediated by retinoic acid, while cellular sensitivity is preferentially correlated to upregulation of short RAR2 transcript variants in response to retinoic acid. The transfection and in vitro translation assay indicated that the short 5'-UTR has no inhibitory effects on translation, while the presence of full-length 5'-UTR inhibited translation by 60%. In addition, no promoter activity was detectable in RAR2 full-length 5'-UTR region. Our data suggest that the RAR2 transcript variants with short 5'-UTR may serve as major transcripts for RAR2 protein translation as well as potential targets for retinoids in breast cancer prevention and therapy studies.