Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR

Saunus, J., French, J.D., Edwards, S.L., Beveridge, D.J., Hatchell, E.C., Wagner, S.A., Stein, S.R., Davidson, A., Simpson, K.J., Francis, G.D., Leedman, P.J. and Brown, M.A. (2008) Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR. Cancer Research, 68 22: 9469-9478. doi:10.1158/0008-5472.CAN-08-1159


 
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Author Saunus, J.
French, J.D.
Edwards, S.L.
Beveridge, D.J.
Hatchell, E.C.
Wagner, S.A.
Stein, S.R.
Davidson, A.
Simpson, K.J.
Francis, G.D.
Leedman, P.J.
Brown, M.A.
Title Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR
Formatted title
Posttranscriptional regulation of the breast cancer susceptibility gene BRCA1 by the RNA binding protein HuR
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
Publication date 2008-11-15
Year available 2008
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-08-1159
Open Access Status Not yet assessed
Volume 68
Issue 22
Start page 9469
End page 9478
Total pages 10
Place of publication Philadelphia, USA
Publisher American Association for Cancer Research
Language eng
Subject C1
060407 Genome Structure and Regulation
111203 Cancer Genetics
920102 Cancer and Related Disorders
920507 Women's Health
1112 Oncology and Carcinogenesis
Abstract BRCA1 is a breast cancer susceptibility gene that is down-regulated in a significant proportion of sporadic breast cancers. BRCA1 is posttranscriptionally regulated by RNA-binding proteins, the identities of which are unknown. HuR is an RNA binding protein implicated in posttranscriptional regulation of many genes and is overexpressed in sporadic breast cancer. To investigate the possibility that these two molecules are functionally linked in breast cancer, we performed bioinformatic analysis of the BRCA1 3' untranslated region (UTR), RNA-protein assays with the HuR protein and the BRCA1 3'UTR, and immunohistochemical analysis of a cohort of breast tumors using antibodies against BRCA1 and HuR. Here, we describe the identification of two predicted HuR-binding sites in the BRCA1 3'UTR, one of which binds specifically to HuR. We also show that this interaction is disrupted by single nucleotide substitutions in the BRCA1 3'UTR and that endogenous HuR protein associates with BRCA1 transcripts in T47D and MCF7 breast cancer cells. Expression of ectopic HuR results in a significant decrease in BRCA1 protein expression and also BRCA1 3'UTR activity. Immunohistochemical analysis revealed that although BRCA1 and HuR expression were associated with some clinicopathologic features of the tumors, there was no statistically significant correlation between BRCA1 and HuR protein expression. These results identify the first posttranscriptional protein regulator of BRCA1 and have implications for understanding BRCA1 regulation in human breast cancer
Keyword BRCA1
HuR
Posttranscriptional Regulation
3'UTR
Breast cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 143037
Institutional Status UQ

 
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