This Article Full Text Full Text (PDF) Supplementary Data Correction (v67,p4535) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakanishi, T. Articles by Ross, D. D. Search for Related Content PubMed PubMed Citation Articles by Nakanishi, T. Articles by Ross, D. D.

Novel 5' Untranslated Region Variants of BCRP mRNA Are Differentially Expressed in Drug-Selected Cancer Cells and in Normal Human Tissues: Implications for Drug Resistance, Tissue-Specific Expression, and Alternative Promoter Usage

¹ The Program in Experimental Therapeutics, Marlene and Stewart Greenebaum Cancer Center; Departments of ² Medicine and ³ Microbiology, University of Maryland School of Medicine; ⁴ Baltimore Veterans Medical Center, Baltimore, Maryland; and ⁵ Department of Interdisciplinary Oncology, Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

Requests for reprints: Takeo Nakanishi, University of Maryland Greenebaum Cancer Center, Room 9-031, Bressler Research Building, 655 West Baltimore Street, Baltimore, MD 21201. Phone: 410-328-3685; Fax: 410-328-6559; E-mail: tnakanishi{at}som.umaryland.edu.

To investigate transcriptional activation of the breast cancer resistance protein gene (BCRP/ABCG2), we examined the 5' untranslated region of BCRP mRNA in cell lines with high BCRP transcriptional activity and in normal tissues. Human choriocarcinoma cells with high endogenous BCRP expression (JAR and BeWo) and human cancer cells (MCF-7 and Igrov1) and their BCRP-overexpressing, drug-selected, multidrug-resistant derivatives (MCF-7/AdrVp, Igrov1/MX3, and Igrov1/T8) were studied. Rapid amplification of 5'-cDNA ends-PCR (5'RACE-PCR) revealed at least three novel forms of the untranslated exon 1 (E1a, E1b, and E1c) that are spliced to a common exon 2, with differential expression of these splice variants in the drug-selected cell lines. Additionally, sequence analysis of the 5'RACE-PCR products revealed multiple transcriptional start sites for each variant, particularly in the drug-selected cells. The E1c isoform predominated in drug-selected MCF-7 cell lines and was translated more efficiently in MCF-7 cells than the E1a isoform. Varying patterns of expression of the exon 1 isoforms were observed in a variety of human tissues, suggesting that tissue-specific alternative promoters of BCRP exist. In summary, we find that BCRP overexpression in the drug-selected cells is accompanied by multiple transcriptional start sites and predominance of the more efficiently translated E1c isoform. The exon 1 variation we observe suggests that alternative promoters of the BCRP gene exist. (Cancer Res 2006; 66(10): 5007-11)

This article has been cited by other articles:

				K. K. W. To, Z. Zhan, T. Litman, and S. E. Bates Regulation of ABCG2 Expression at the 3' Untranslated Region of Its mRNA through Modulation of Transcript Stability and Protein Translation by a Putative MicroRNA in the S1 Colon Cancer Cell Line Mol. Cell. Biol., September 1, 2008; 28(17): 5147 - 5161. [Abstract] [Full Text] [PDF]

				S. Kreth, C. Ledderose, I. Kaufmann, G. Groeger, and M. Thiel Differential expression of 5'-UTR splice variants of the adenosine A2A receptor gene in human granulocytes: identification, characterization, and functional impact on activation FASEB J, September 1, 2008; 22(9): 3276 - 3286. [Abstract] [Full Text] [PDF]

				B. Poonkuzhali, J. Lamba, S. Strom, A. Sparreboom, K. Thummel, P. Watkins, and E. Schuetz Association of Breast Cancer Resistance Protein/ABCG2 Phenotypes and Novel Promoter and Intron 1 Single Nucleotide Polymorphisms Drug Metab. Dispos., April 1, 2008; 36(4): 780 - 795. [Abstract] [Full Text] [PDF]

				K. K.W. To, O. Polgar, L. M. Huff, K. Morisaki, and S. E. Bates Histone Modifications at the ABCG2 Promoter following Treatment with Histone Deacetylase Inhibitor Mirror Those in Multidrug-Resistant Cells Mol. Cancer Res., January 1, 2008; 6(1): 151 - 164. [Abstract] [Full Text] [PDF]

				Correction: Differential Expression of 5'UTR Variants of BCRP mRNA Cancer Res., May 1, 2007; 67(9): 4535 - 4535. [Full Text] [PDF]

				M. Wang Extending the Good Diet, Good Health Paradigm: Modulation of Breast Cancer Resistance Protein (BCRP) by Flavonoids Toxicol. Sci., April 1, 2007; 96(2): 203 - 205. [Full Text] [PDF]

				Y. Zong, S. Zhou, S. Fatima, and B. P. Sorrentino Expression of Mouse Abcg2 mRNA during Hematopoiesis Is Regulated by Alternative Use of Multiple Leader Exons and Promoters J. Biol. Chem., October 6, 2006; 281(40): 29625 - 29632. [Abstract] [Full Text] [PDF]