Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene

Bailey-Dell, Kimberly J.; Hassel, Bret A.; Doyle, L. Austin; Ross, Douglas D.

doi:10.1016/s0167-4781(01)00270-6

Cited by 208 publications

(188 citation statements)

References 20 publications

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“…37 BCRP is transcribed by a TATA boxless promoter with multiple Sp1 sites and a CCAAT box. 34,39 We examined Sp1 mRNA expression by using semiquan- titative RT-PCR in PC-6 and PC-6/SN2-5H cells. The results indicated that the expression of Sp1 was increased more in PC-6/SN2-5H cells than in PC-6 cells (data not shown), supporting the belief that Sp1 also contributes to BCRP re-expression.…”

Section: Discussionmentioning

confidence: 99%

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Methylation status of breast cancer resistance protein detected by methylation‐specific polymerase chain reaction analysis is correlated inversely with its expression in drug‐resistant lung cancer cells

Nakano

Nakamura

Soda

et al. 2008

Cancer

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It is increasingly difficult to choose the proper tests to investigate an abnormal laboratory result, delaying the time to reach the correct diagnosis and increasing the cost of care. A wrong choice may also lead to clinically significant errors, which can be life threatening. To show how errors in test selection occur in routine medical practice, the authors describe an algorithm to evaluate patients with a prolonged activated partial thromboplastin time (PTT) and a normal prothrombin time. This exercise challenges the commonly held belief that errors in laboratory utilization occur primarily with esoteric and/or genetic testing, rather than in patients with common abnormalities such as a prolonged PTT. Am. J. Hematol. 2013. © 2012 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

“…The promoter region ranging from nucleotide (nt) 21381 to nt 1261 with respect to the transcription initiation site of BCRP (GenBank Accession no. AF151530) 34 was divided into 5 segments (A through E). Primer pairs for both PCR and direct DNA sequencing were designed in each region (Table 1).…”

Section: Flow Cytometrymentioning

confidence: 99%

Methylation status of breast cancer resistance protein detected by methylation‐specific polymerase chain reaction analysis is correlated inversely with its expression in drug‐resistant lung cancer cells

Nakano

Nakamura

Soda

et al. 2008

Cancer

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“…The ABCG2 gene spans over 66 kb and is made up of 16 exons and 15 introns; the resulting protein is 655 amino acids long and runs as a 72 kDa protein on an SDS-PAGE gel under reducing conditions (23). Fluorescence in situ hybridization studies with a bacterial artificial chromosome probe containing ABCG2 localized the gene to chromosome 4q21-4q22 in a cell with a normal chromosome 4 (24).…”

Section: Discussionmentioning

confidence: 99%

Functional expression and characterization in Xenopus laevis oocytes of the ABCG2 transporter derived from A549 human lung adenocarcinoma cells

Shin¹

2011

Oncol Rep

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Abstract.We cloned the ATP-binding cassette sub-family G member 2 (ABCG2) transporter, the most recently identified among several major human multidrug-resistance pumps, from A549 human lung adenocarcinoma cells in order to characterize its function and substrate specificity. In a previous report, we confirmed that a stem cell-like side population of A549 cells highly expressed the ABCG2 gene and had a unique ability to resist the anticancer drug methotrexate (MTX). In this study, ABCG2 cDNA was cloned by RT-PCR and converted into cRNA by an in vitro transcription system for expression in Xenopus laevis (X. laevis) oocytes. The transcribed cRNA of the ABCG2 gene was injected into the oocytes under the absence of cofactors or heterologous partner proteins or some lipids from the media. A high expression of ABCG2 was observed on the oocyte surface by immunofluorescence and confocal laser microscopy. We tested the functional effect of ABCG2 expression on drug efflux by directly injecting MTX into X. laevis oocytes. The drug concentration within the oocytes was quantified with LC-MS/MS; the analysis showed that the accumulation of MTX was significantly decreased in the X. laevis oocytes expressing ABCG2 compared with the control oocytes not expressing ABCG2. These findings show that the ABCG2 protein has an important role in the efflux of MTX through the cell membrane of X. laevis oocytes. Therefore, it might be that ABCG2, abundantly expressed in the stem cell population of A549 cells, can modulate resistance to MTX in lung cancer therapy.

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“…This phenomenon was investigated by several groups in recent years, both in the case of human and mice ABCG2, and led to the identification of at least two exon 1 isoforms and their corresponding promoter regions besides the one described initially [23]. All exon 1 sequences contribute to the 5' UTR of the mRNA, and are spliced to a common exon 2 where the translation initiation codon is localized.…”

Section: Possible Upstream Alternative Translation Regulations: the Pmentioning

confidence: 99%

“…Subsequent work, aiming to study the ABCG2 promoter structure and regulation, predicted a number of putative transcription factor binding sites (e.g. : AP1, AP2 and several Sp1 sites) and described a CpG island but no TATA-box in the investigated promoter region [23]. A later study, however, described the presence of two other potential transcriptional initiation sites, whichanalogously to the mouse ortholog [24] -result in the formation of two additional leader exons and thereby two mRNA species with different 5' untranslated regions (5' UTRs) [25].…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of the ABCG2 5′ non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection

Sándor

Jordanidisz

Schamberger

et al. 2016

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Functional characterization of the ABCG2 5' non-coding exon variants: stem cell specificity, translation efficiency and the influence of drug selection, BBA -Gene Regulatory Mechanisms (2016Mechanisms ( ), doi: 10.1016Mechanisms ( /j.bbagrm.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 Abstract ABCG2 is a multidrug transporter with wide substrate specificity, and is believed to protect several cell types from various xenobiotics and endobiotics. This "guardian" function is important in numerous cell types and tissue barriers but becomes disadvantageous by being responsible for the multidrug resistance phenotype in certain tumor cells. ABCG2 regulation at the protein level has already been extensively studied, however, regulation at the mRNA level, especially the functional role of the various 5' untranslated exon variants (5' UTRs) has been elusive. In the present work, we describe a comprehensive characterization of four ABCG2 mRNA variants with different exon 1 sequences, investigate drug inducibility, stem cell specificity, mRNA stability, and translation efficiency. Although certain variants (E1B and E1C) are considered as "constitutive" mRNA isoforms, we show that chemotoxic drugs significantly alter the expression pattern of distinct ABCG2 mRNA isoforms. When examining human embryonic stem cell lines, we provide evidence that variant E1A has an expression pattern coupled to undifferentiated stem cell stage, as its transcript level is regulated parallel to mRNAs of Oct4 and Nanog pluripotency marker genes. When characterizing the four exon 1 variants we found no significant differences in terms of mRNA stabilities and half-lives of the isoforms. In contrast, variant E1U showed markedly lower translation efficiency both at the total protein level or regarding the functional presence in the plasma membrane. Taken together, these results indicate that the different 5' UTR variants play an important role in cell type specific regulation and fine tuning of ABCG2 expression.

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Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene

Cited by 208 publications

References 20 publications

Methylation status of breast cancer resistance protein detected by methylation‐specific polymerase chain reaction analysis is correlated inversely with its expression in drug‐resistant lung cancer cells

Methylation status of breast cancer resistance protein detected by methylation‐specific polymerase chain reaction analysis is correlated inversely with its expression in drug‐resistant lung cancer cells

Functional expression and characterization in Xenopus laevis oocytes of the ABCG2 transporter derived from A549 human lung adenocarcinoma cells

Functional characterization of the ABCG2 5′ non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection

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