Trps1 is associated with the multidrug resistance of osteosarcoma by regulating MDR1 gene expression

Ming Jia; Jing Hu; Weiwei Li; Peng Su; Hui Zhang; Xiaofang Zhang; Gengyin Zhou

doi:10.1016/j.febslet.2014.01.041

Trps1 is associated with the multidrug resistance of osteosarcoma by regulating MDR1 gene expression

FEBS Lett. 2014 Mar 3;588(5):801-10. doi: 10.1016/j.febslet.2014.01.041. Epub 2014 Jan 31.

Authors

Ming Jia¹, Jing Hu², Weiwei Li³, Peng Su⁴, Hui Zhang⁵, Xiaofang Zhang⁶, Gengyin Zhou⁷

Affiliations

¹ Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: laomao285535@163.com.
² Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: waterfall_1988@aliyun.com.
³ Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: liweiweizhao@163.com.
⁴ Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: supeng820125@163.com.
⁵ Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: huizhang2576@gmail.com.
⁶ Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: zdpxf2317@yahoo.cn.
⁷ Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: zhougy@sdu.edu.cn.

PMID: 24491996
DOI: 10.1016/j.febslet.2014.01.041

Abstract

Multidrug resistance (MDR) is a significant clinical problem in the chemotherapy of osteosarcoma and has been linked to the cellular expression of several multidrug-efflux transporters such as MDR1/P-gp. Our inhibition of the transcription factor Trps1 led to repression of MDR1/P-gp while its overexpression resulted in upregulation of MDR1/P-gp. Flow cytometric analysis suggested Trps1 increased the release of several anti-cancer drugs, thus decreasing their accumulation. Immunohistochemical analysis of clinical samples indicated that the expression of Trps1 directly correlated with MDR1/P-gp. Trps1 inhibited TGFbeta-1 and directly bound to the MDR1 promoter. Our data demonstrate a role for Trps1 in the regulation of MDR1 expression in osteosarcoma.

Keywords: CHIP; Chemotherapy; MDR1; Multidrug resistance; Osteosarcoma; P-gp; TGFbeta-1; TRPS1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Antibiotics, Antineoplastic / pharmacology
Base Sequence
Binding Sites
Bone Neoplasms / drug therapy
Bone Neoplasms / genetics
Bone Neoplasms / metabolism*
Cell Line, Tumor
Cell Survival / drug effects
DNA-Binding Proteins / physiology*
Doxorubicin / pharmacology
Drug Resistance, Neoplasm*
Gene Expression
Gene Expression Regulation, Neoplastic
Humans
Inhibitory Concentration 50
Molecular Sequence Data
Osteosarcoma / drug therapy
Osteosarcoma / genetics
Osteosarcoma / metabolism*
Promoter Regions, Genetic
Protein Binding
RNA, Messenger / genetics
RNA, Messenger / metabolism
Repressor Proteins
Transcription Factors / physiology*

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Antibiotics, Antineoplastic
DNA-Binding Proteins
RNA, Messenger
Repressor Proteins
TRPS1 protein, human
Transcription Factors
Doxorubicin