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Regulation of the multidrug transpor...

Chen, (Gang) G. Kevin.

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Regulation of the multidrug transporter MDR1 (ABCB1) gene.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Regulation of the multidrug transporter MDR1 (ABCB1) gene./
Author:	Chen, (Gang) G. Kevin.
Description:	232 p.
Notes:	Adviser: Branimir I. Sikic.
Contained By:	Dissertation Abstracts International63-04B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3048500
ISBN:	0493628312

Regulation of the multidrug transporter MDR1 (ABCB1) gene.
Chen, (Gang) G. Kevin.

Regulation of the multidrug transporter MDR1 (ABCB1) gene. - 232 p.

Adviser: Branimir I. Sikic.

Thesis (Ph.D.)--Stanford University, 2002.

We studied MDR1 gene regulation in multidrug resistant (MDR) cellular models. The MDR phenotype is mediated by the multidrug transporter P-glycoprotein (P-gp), encoded by the <italic>MDR</italic>1 gene (also known as <italic> ABCB</italic>1). Our data provide direct evidence supporting that selection of spontaneous mutants was associated with the development of the MDR phenotype. We proposed a novel mechanism elucidating the origin of MDR cells under a stringent selection, by which an interplay between spontaneous mutants (with activation of the upstream transcripts) and induced alterations may be required. Thus, activation of far upstream transcripts may be an important mechanism for acquired <italic>MDR</italic>1 expression in some cancer cells. To investigate the induction mechanisms of <italic>MDR</italic>1 expression, we focused on the role of C/EBPβ (NF-IL6) (a member of the basic leucine zipper family, bZIP) in regulating <italic>MDR</italic>1 in MCF-7 cells. Our results suggest that alteration of expression or function of C/EBPβ may play an important role in <italic>MDR</italic>1 gene regulation. The mechanisms of <italic> MDR</italic>1 activation by C/EBPβ may be <italic>via</italic> C/EBPβ recruitment of chromatin-remodeling factors (e.g., hBrm) and its interactions with an inverted CCAAT-box (Y-box). In summary, our data provide both biochemical and genetic evidence regarding <italic>MDR</italic>1 gene regulation in human cancer cells. <italic>MDR</italic>1 expression could be either induced by transcription factors or selected due to the intrinsic genomic instability of cancer cells. Understanding the molecular details of <italic>MDR</italic>1 regulation may provide rational approaches to modulating <italic>MDR</italic>1/P-pg expression.

ISBN: 0493628312Subjects--Topical Terms:

1017686
Biology, Cell.

Regulation of the multidrug transporter MDR1 (ABCB1) gene.
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020 $a 0493628312
035 $a (UnM)AAI3048500
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100 1 $a Chen, (Gang) G. Kevin. $3 1251274
245 1 0 $a Regulation of the multidrug transporter MDR1 (ABCB1) gene.
300 $a 232 p.
500 $a Adviser: Branimir I. Sikic.
500 $a Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 1694.
502 $a Thesis (Ph.D.)--Stanford University, 2002.
520 $a We studied MDR1 gene regulation in multidrug resistant (MDR) cellular models. The MDR phenotype is mediated by the multidrug transporter P-glycoprotein (P-gp), encoded by the <italic>MDR</italic>1 gene (also known as <italic> ABCB</italic>1). Our data provide direct evidence supporting that selection of spontaneous mutants was associated with the development of the MDR phenotype. We proposed a novel mechanism elucidating the origin of MDR cells under a stringent selection, by which an interplay between spontaneous mutants (with activation of the upstream transcripts) and induced alterations may be required. Thus, activation of far upstream transcripts may be an important mechanism for acquired <italic>MDR</italic>1 expression in some cancer cells. To investigate the induction mechanisms of <italic>MDR</italic>1 expression, we focused on the role of C/EBPβ (NF-IL6) (a member of the basic leucine zipper family, bZIP) in regulating <italic>MDR</italic>1 in MCF-7 cells. Our results suggest that alteration of expression or function of C/EBPβ may play an important role in <italic>MDR</italic>1 gene regulation. The mechanisms of <italic> MDR</italic>1 activation by C/EBPβ may be <italic>via</italic> C/EBPβ recruitment of chromatin-remodeling factors (e.g., hBrm) and its interactions with an inverted CCAAT-box (Y-box). In summary, our data provide both biochemical and genetic evidence regarding <italic>MDR</italic>1 gene regulation in human cancer cells. <italic>MDR</italic>1 expression could be either induced by transcription factors or selected due to the intrinsic genomic instability of cancer cells. Understanding the molecular details of <italic>MDR</italic>1 regulation may provide rational approaches to modulating <italic>MDR</italic>1/P-pg expression.
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