Steroid receptor RNA activator protein (SRAP) expression as a prognostic factor in ER+ human breast tumors

Yan, Yongping; Penner, Carla; Skliris, Georgios; Cooper, Charlton; Nugent, Zoann; Blanchard, Anne; Hamedani, Mohammad K.; Wang, Xuemei; Myal, Yvonne; Murphy, Leigh C.; Leygue, Etienne

doi:10.1007/s00432-013-1485-2

Cited by 10 publications

(8 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was also attenuated when recombinant SRAP protein was added as a competitive inhibitor of antibody binding (bottom rows). While this manuscript was in preparation, another group published results on the localization of endogenous SRAP in MCF-7 cells, using different antibodies [20]; our results are in agreement with theirs.…”

Section: Resultssupporting

confidence: 89%

“…SRAP is expressed at relatively high levels in cells, and several independent studies show it is partitioned in part to the nucleus ([8, 19, 20] and this work). Arguably, an intriguing hint may come from the structural similarity of the SRAP carboxy-terminal domain to that of the yeast PRP18 protein—intriguing because, although the 5-helix bundle is a very simple fold, these are the only two proteins in the protein structure database that share it.…”

Section: Discussionmentioning

confidence: 72%

“…SRAP resides in part in the nucleus ([8, 19, 20] and this work), suggesting it is likely to have a nuclear function. The structural similarity of its carboxy-terminal domain to that of PRP18 suggests it may be involved in the assembly of multisubunit complexes through specific protein-protein interactions.…”

Section: Discussionmentioning

confidence: 89%

See 2 more Smart Citations

Structure and Function of Steroid Receptor RNA Activator Protein, the Proposed Partner of SRA Noncoding RNA

McKay

Barthel

et al. 2014

Journal of Molecular Biology

View full text Add to dashboard Cite

In a widely accepted model, the steroid receptor RNA activator protein (SRA protein; SRAP) modulates the transcriptional regulatory activity of SRA RNA by binding a specific stem-loop of SRA. We first confirmed that SRAP is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, where it is expressed at the level of about 105 molecules/cell. However, our SRAP-RNA binding experiments, both in vitro with recombinant protein and in cultured cells with plasmid-expressed protein and RNA, did not reveal a specific interaction between SRAP and SRA. We determined the crystal structure of the carboxy-terminal domain of human SRAP and found that it does not have the postulated RRM (RNA recognition motif). The structure is a five-helix bundle that is distinct from known RNA-binding motifs and instead is similar to the carboxy-terminal domain of the yeast spliceosome protein PRP18, which stabilizes specific protein-protein interactions within a multisubunit mRNA splicing complex. SRA binding experiments with this domain gave negative results. Transcriptional regulation by SRA/SRAP was examined with siRNA knockdown. Effects on both specific estrogen-responsive genes and genes identified by RNA-seq as candidates for regulation were examined in MCF-7 cells. Only a small effect (~20% change) on one gene resulting from depletion of SRA/SRAP could be confirmed. We conclude that the current model for SRAP function must be re-evaluated; we suggest SRAP may function in a different context to stabilize specific intermolecular interactions in the nucleus.

show abstract

Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 72%

See 1 more Smart Citation

Structure and Function of Steroid Receptor RNA Activator Protein, the Proposed Partner of SRA Noncoding RNA

McKay

Barthel

et al. 2014

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…Several SNPs (rs10463297, rs801460) located in whole SRA sequence has been identified to increase cancerous risk [81]. SRA not only acts as a regulatory lncRNA, but also codes for the SRA protein (SRAP), which is highly expressed in primary breast tumors as well [82, 83]. The balance between fully-spliced SRAP-coding RNA and intron-1-containing non-coding SRA RNA might characterize the specific phenotypes of breast cancer and modulate tumorigenesis and progression by regulating the expression of specific genes [84].…”

Section: Sramentioning

confidence: 99%

Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication

Xiong

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs), which occupy nearly 98% of genome, have crucial roles in cancer development, including breast cancer. Breast cancer is a disease with high incidence. Despite of recent progress in understanding the molecular mechanisms and combined therapy strategies, the functions and mechanisms of lncRNAs in breast cancer remains unclear. This review presents the currently basic knowledge and research approaches of lncRNAs. We also highlight the latest advances of seven classic lncRNAs and three novel lncRNAs in breast cancer, elucidating their mechanisms and possible therapeutic targets. Additionally, association between lncRNA and specific molecular subtype of breast cancer is reported. Lastly, we briefly delineate the potential roles of lncRNAs in clinical applications as biomarkers and treatment targets.

show abstract

“…IHC analyses of such TMAs have the great advantage to minimalize all the intra-laboratory differences in staining procedures, as well as the inter‑observer evaluation variability. Moreover, TMAs can even be constructed from paraffin needle biopsy specimens and also allow testing the expression of biomarkers on the following slides of a constructed TMA block for studying markers co-expressions [6,7,8,9,10,11,12,13]. …”

Section: Introduction: Tma Technology and Statistical Considerationsmentioning

confidence: 99%

Re-Punching Tissue Microarrays Is Possible: Why Can This Be Useful and How to Do It

et al. 2015

View full text Add to dashboard Cite

Tissue microarray (TMA) methodology allows the concomitant analysis of hundreds of tissue specimens arrayed in the same manner on a recipient block. Subsequently, all samples can be processed under identical conditions, such as antigen retrieval procedure, reagent concentrations, incubation times with antibodies/probes, and escaping the inter-assays variability. Therefore, the use of TMA has revolutionized histopathology translational research projects and has become a tool very often used for putative biomarker investigations. TMAs are particularly relevant for large scale analysis of a defined disease entity. In the course of these exploratory studies, rare subpopulations can be discovered or identified. This can refer to subsets of patients with more particular phenotypic or genotypic disease with low incidence or to patients receiving a particular treatment. Such rare cohorts should be collected for more specific investigations at a later time, when, possibly, more samples of a rare identity will be available as well as more knowledge derived from concomitant, e.g., genetic, investigations will have been acquired. In this article we analyze for the first time the limits and opportunities to construct new TMA blocks using tissues from older available arrays and supplementary donor blocks. In summary, we describe the reasons and technical details for the construction of rare disease entities arrays.

show abstract

Steroid receptor RNA activator protein (SRAP) expression as a prognostic factor in ER+ human breast tumors

Abstract: Overall, our data suggest the existence in breast tumor tissue of multiple SRAP-like peptides. Assessing their expression in primary breast tumors can predict clinical outcome in ER+ breast cancer patients.

Cited by 10 publications

References 26 publications

Structure and Function of Steroid Receptor RNA Activator Protein, the Proposed Partner of SRA Noncoding RNA

Structure and Function of Steroid Receptor RNA Activator Protein, the Proposed Partner of SRA Noncoding RNA

Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication

Re-Punching Tissue Microarrays Is Possible: Why Can This Be Useful and How to Do It

Contact Info

Product

Resources

About