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PMID: 23251525 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Microarray-assisted pathway analysis identifies MT1X & NFκB as mediators of TCRP1-associated resistance to cisplatin in oral squamous cell carcinoma.

PloS one ·Vol. 7 ·No. 12 ·2012-00-00 ·Pages e51413

Peng B, Gu Y, Xiong Y, Zheng G, He Z

Abstract

We recently reported that TCRP1, a novel multidrug-resistance associated human gene, can mediate cisplatin resistance in OSCC cells. However, the molecular mechanism underlying this role of TCRP1 remained to be elucidated. In this study, by using Human Toxicology and Drug Resistance Microarray, we identified 30 genes with significantly different expression levels between Tca/PYM and TCRP1 knockdown cell lines. Co-immunoprecipitation experiments and GST-pull down assays showed that metallothionein1X (MT1X) and Akt interact with TCRP1. siRNA-mediated knockdown of TCRP1 and MT1X was found to sensitize cells to cisplatin, leading to increased apoptosis and inhibition of cell proliferation. These functions of TCRP1 may be caused at least in part via activation of the PI3K/Akt/NF-κB signaling pathway. Taken together, our findings indicate that TCRP1 may be an important drug target for improvement of the treatment and survival of patients with oral squamous cell carcinoma.

MeSH Terms
Antineoplastic Agents/pharmacology,therapeutic use Apoptosis/genetics Base Sequence Blotting, Western Carcinoma, Squamous Cell/drug therapy,metabolism Cell Line, Tumor Cisplatin/pharmacology,therapeutic use DNA Primers Drug Resistance, Neoplasm Gene Knockdown Techniques Humans Metallothionein/genetics,physiology Mouth Neoplasms/drug therapy,metabolism NF-kappa B/metabolism Oligonucleotide Array Sequence Analysis Proteins/genetics,metabolism Real-Time Polymerase Chain Reaction
Chemicals
Antineoplastic Agents DNA Primers NF-kappa B Proteins metallothionein1X , human tongue cancer resistance-associated protein 1, human Metallothionein Cisplatin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Peng Bo
Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, Guangdong, China.
Gu Yixue
Xiong Yan
Zheng Guopei
He Zhimin
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0051413
Published
2012-00-00
Epub
2012-00-10
Pages
e51413
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3519677
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0051413 PMC Full Text View journal details
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