title: β-arrestin 2 is associated with multidrug resistance in breast cancer cells through regulating MDR1 gene expression.
abstract: Mutidrug resistance (MDR) severely blocks the successful management of breast cancer. Overexpression of MDR1/p-gp accounts for the major factor in the development of MDR. β-arrestin 2 has been reported to widely involve in multiple aspects of tumor development. In order to verify whether β-arrestin 2 regulates mutidrug resistance in breast cancer, we analyzed the protein expression levels of β-arrestin 2 and MDR1/p-gp by immunohistochemistry in 106 paraffin-embedded human breast tissue samples. There was a positive correlation between β-arrestin 2 and MDR1/p-gp protein expression (P = 0.016). Changes in MDR1/p-gp mRNA and protein levels were examined by quantitative real-time reverse polymerase chain reaction (qRT-PCR) and western blotting. Silencing of β-arrestin 2 evidently down-regulated the expression of MDR1/p-gp in transfected ADM cells. In contrast, overexpression of β-arrestin 2 had the opposite changes in MDA-MB-231 and MCF-7 cells. MTS assay revealed that silencing of β-arrestin 2 increased the sensitivity to anti-cancer drugs to some extent. On the other hand, overexpression of β-arrestin 2 had the opposite effects. Our above data demonstrate that β-arrestin 2 plays a vital role in the regulation of MDR1/p-gp expression in Breast cancer.
authors.affiliation: Department of Pathology, Shandong University School of Medicine 44 Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Pathology, Qilu Hospital of Shandong University 107 Wenhua Xi Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shandong University School of Medicine 44 Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology, Qilu Hospital of Shandong University 107 Wenhua Xi Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.affiliation: Department of Pathology, Shandong University School of Medicine 44 Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shandong University School of Medicine 44 Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Pathology, Shan Dong Provincial Hospital 324 Five Weft Seven Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Qilu Hospital of Shandong University 107 Wenhua Xi Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, Shandong University School of Medicine 44 Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C513055:ABCB1 protein, human; C000605254:ARRB2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D019390:Arrestins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
keywords: MDR1/p-gp; breast cancer; chemotherapy; mutidrug resistance (MDR); β-arrestin 2