The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

BMC Cancer

Research Article

Robert Calaluce¹  Joseph D Magee¹  Jing Chen¹  Matthew M Gubin¹  Ulus Atasoy²  J Wade Davis³  Myriam Gorospe⁴  Yuki Kuwano⁴ 

[1] Departments of Surgery, University of Missouri, One Hospital Drive, 65212, Columbia, Missouri, USA;Departments of Surgery, University of Missouri, One Hospital Drive, 65212, Columbia, Missouri, USA;Molecular Microbiology and Immunology, One Hospital Drive, 65212, Columbia, Missouri, USA;Child Health, University of Missouri, One Hospital Drive, 65212, Columbia, Missouri, USA;Health Management and Informatics, University of Missouri, 187 Galena Hall, 65212, Columbia, Missouri, USA;Statistics, University of Missouri, 146 Middlebush Hall, 65211, Columbia, Missouri, USA;National Institute of Aging, 251 Bayview Boulevard, 21224, Baltimore, Maryland, USA;

关键词: Gene Ontology;    Posttranscriptional Gene Regulation;    Acquire Tamoxifen Resistance;    Entrez Identifier;   

DOI  :  10.1186/1471-2407-10-126

 received in 2009-09-30, accepted in 2010-04-06,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs).MethodsThe ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established.ResultsWe used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis.ConclusionThis is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.

【 授权许可】

Unknown   
© Calaluce et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.