Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance (MDR1) gene

被引：52

作者：

Antonio-Andres, Gabriela ^{[1
]}

Rangel-Santiago, Jesus ^{[1
]}

Tirado-Rodriguez, Belen ^{[1
]}

Martinez-Ruiz, Gustavo U. ^{[1
,2
]}

Klunder-Klunder, Miguel ^{[3
]}

Vega, Mario I. ^{[4
,5
]}

Lopez-Martinez, Briceida ^{[6
]}

Jimenez-Hernandez, Elva ^{[7
]}

Torres Nava, Jose ^{[7
]}

Medina-Sanson, Aurora ^{[8
]}

Huerta-Yepez, Sara ^{[1
]}

机构：

[1] Hosp Infantil Mexico Dr Federico Gomez, Unidad Invest Enfermedades Oncol, Dr Marquez 262, Mexico City 06720, DF, Mexico

[2] Univ Nacl Autonoma Mexico, Fac Med, Mexico City, DF, Mexico

[3] Hosp Infantil Mexico Dr Federico Gomez, Dept Invest Salud Comunitaria, Mexico City, DF, Mexico

[4] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, VA West Los Angeles Med Ctr BBRI, Dept Med,Hematol Oncol Div,Med Ctr, Los Angeles, CA 90024 USA

[5] UIMEO, Siglo XXI Natl Med Ctr, IMSS, Mol Signal Pathway Canc Lab,Oncol Hosp, Mexico City, DF, Mexico

[6] Hosp Infantil Mexico Dr Federico Gomez, Lab Cent, Mexico City, DF, Mexico

[7] Hosp Infantil Moctezuma, Serv Hematooncol, Mexico City, DF, Mexico

[8] Hosp Infantil Mexico Dr Federico Gomez, Dept Hematooncol, Mexico City, DF, Mexico

来源：

LEUKEMIA & LYMPHOMA | 2018年 / 59卷 / 11期

关键词：

Acute lymphoblastic leukemia; MDR1; YY1; children; chemoresistance; MESSENGER-RNA EXPRESSION; P-GLYCOPROTEIN; UP-REGULATION; PERIPHERAL-BLOOD; PROGNOSTIC-SIGNIFICANCE; CELL-LINE; YIN-YANG-1; LEUKEMIA; POLYMORPHISMS; ACTIVATION;

D O I：

10.1080/10428194.2018.1448083

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function. The clinical roles of YY1 and MDR1 expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and MDR1 expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of MDR1. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.

引用

页码：2628 / 2638

页数：11

共 63 条

[1]

Abolhoda A, 1999, CLIN CANCER RES, V5, P3352

[2]

Addeo R, 2005, CANCER BIOL THER, V4, P32

[3]

P-glycoprotein: from genomics to mechanism [J].

Ambudkar, SV ;

Kimchi-Sarfaty, C ;

Sauna, ZE ;

Gottesman, MM .

ONCOGENE, 2003, 22 (47) :7468-7485

[4]

Biochemical, cellular, and pharmacological aspects of the multidrug transporter [J].

Ambudkar, SV ;

Dey, S ;

Hrycyna, CA ;

Ramachandra, M ;

Pastan, I ;

Gottesman, MM .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 :361-398

[5]

Chemotherapeutic drugs sensitize cancer cells to TRAIL-mediated apoptosis: up-regulation of DR5 and inhibition of Yin Yang 1 [J].

Baritaki, Stavroula ;

Huerta-Yepez, Sara ;

Sakai, Toshiyuki ;

Spandidos, Demetrios A. ;

Bonavida, Benjamin .

MOLECULAR CANCER THERAPEUTICS, 2007, 6 (04) :1387-1399

[6]

Cao QX, 1996, AM J HEMATOL, V52, P329, DOI 10.1002/1096-8652(199608)52:4<329::AID-AJH2830520402>3.0.CO

[7]

2-Y

[8]

INDUCTION OF MULTIDRUG RESISTANCE IN HUMAN-CELLS BY TRANSIENT EXPOSURE TO DIFFERENT CHEMOTHERAPEUTIC DRUGS [J].

CHAUDHARY, PM ;

RONINSON, IB .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (08) :632-639

[9]

CHIN KV, 1990, J BIOL CHEM, V265, P221

[10]

Comerford KM, 2002, CANCER RES, V62, P3387

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