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BMC Cancer
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

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

Authors: Robert Calaluce, Matthew M Gubin, J Wade Davis, Joseph D Magee, Jing Chen, Yuki Kuwano, Myriam Gorospe, Ulus Atasoy

Published in: BMC Cancer | Issue 1/2010

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Abstract

Background

The 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).

Methods

The 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.

Results

We 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.

Conclusion

This 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.
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Metadata
Title
The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer
Authors
Robert Calaluce
Matthew M Gubin
J Wade Davis
Joseph D Magee
Jing Chen
Yuki Kuwano
Myriam Gorospe
Ulus Atasoy
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-126

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