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Molecular Cancer

, 9:311

First Online: 07 December 2010Received: 22 August 2010Accepted: 07 December 2010

Abstract

BackgroundMCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes.

ResultsMCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 MDM2, Pirh2, and Cop1 are constantly stimulated by MCT-1 oncoprotein.

ConclusionsThe oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development.

List of abbreviationsMCT-1multiple copies in T-cell malignancy 1

bpbase pair

mRNAmessenger RNA

shRNAshort hairpin RNA

NFQnon-fluorescent quencher

FAM5-carboxyfluorescein

PBSphosphate-buffered saline

HRPhorseradish peroxidase

ChIPchromatin immunoprecipitation

EMSAelectrophoretic mobility shift assay

qRT-PCRquantitative real-time polymerase chain reaction

Lucfirefly luciferase

Abantibody

minminute

HandEhematoxylin and eosin

ECLenhanced chemiluminescence

ETOetoposide.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-9-311 contains supplementary material, which is available to authorized users.

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Autor: Ravi Kasiappan - Hung-Ju Shih - Meng-Hsun Wu - ChikOn Choy - Tai-Du Lin - Linyi Chen - Hsin-Ling Hsu

Fuente: https://link.springer.com/







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