Article

Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer

Department of Laboratory Medicine, Center for Molecular Pathology, Malmö University Hospital, Lund University, Malmö, Sweden.
Modern Pathology (Impact Factor: 6.36). 10/2009; 22(12):1564-74. DOI: 10.1038/modpathol.2009.124
Source: PubMed

ABSTRACT Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n=1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (P<0.001), small tumors (P<0.001), estrogen receptor (ER) positivity (P<0.001) and Ki-67 negativity (P<0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P=0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors.

Download full-text

Full-text

Available from: Olle Stål, May 05, 2014
0 Followers
 · 
130 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The RNA-binding motif protein 3 (RBM3) was initially discovered as a putative cancer biomarker based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). We previously reported an association between high expression of RBM3 and prolonged survival in breast and epithelial ovarian cancer (EOC). Because the function of RBM3 has not been fully elucidated, the aim of this study was to use gene set enrichment analysis to identify the underlying biologic processes associated with RBM3 expression in a previously analyzed EOC cohort (cohort 1, n = 267). This revealed an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity. RBM3-regulated genes were subsequently screened in the HPA to select for putative prognostic markers, and candidate proteins were analyzed in the ovarian cancer cell line A2780, whereby an up-regulation of Chk1, Chk2, and MCM3 was demonstrated in siRBM3-treated cells compared to controls. The prognostic value of these markers was assessed at the messenger RNA level in cohort 1 and the protein level in an independent EOC cohort (cohort 2, n = 154). High expression levels of Chk1, Chk2, and MCM3 were associated with a significantly shorter survival in both cohorts, and phosphorylated Chk2 was an adverse prognostic marker in cohort 2. These results uncover a putative role for RBM3 in DNA damage response, which might, in part, explain its cisplatin-sensitizing properties and good prognostic value in EOC. Furthermore, it is demonstrated that Chk1, Chk2, and MCM3 are poor prognostic markers in EOC.
    Translational oncology 08/2011; 4(4):212-21. DOI:10.1593/tlo.11106 · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary form only given. We present a space-domain analogy of the rotating quarter waveplate method. Our method is based on a space-varying waveplate, which we realized as a computer-generated space-variant subwavelength dielectric grating. By performing a spatial Fourier analysis of the intensity transmitted through this polarization grating followed by an analyzer, we can measure all four Stokes parameter simultaneously, thereby enabling real-time polarimetry of polarized and partially polarized beams.
    Lasers and Electro-Optics, 2002. CLEO '02. Technical Digest. Summaries of Papers Presented at the; 02/2002
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is significant need for well-characterized antibodies to the spectrum of human proteins encoded by the genome. Advances in tissue-based proteomic profiling have led to the discovery of many candidate molecular biomarkers and therapeutic targets for which development of clinical assays is depending on high quality antibodies. We developed an antibody validation approach for screening of new mAbs. We utilized a multi-stage approach of protein array and immunohistochemistry. In the first phase, we screened the NCI60 panel of cell lines by means of protein array and select antibodies based on concordance of mRNA expression to protein array signal. Results of this assay are used to predict antibody titer for immunohistochemistry on the NCI60 cell lines, presented as a tissue microarray. In the final stage, we created a tissue-based protein expression map by performing immunohistochemistry on a multi-tumor tissue microarray. The success rate of this systematic antibody-screening tool was approximately 93% as measured by the results from the protein array. Data from the NCI60 protein array could be used to predict antibody titer for immunohistochemistry, improving the success rate of immunohistochemical assay development. The presented strategy of antibody validation and characterization can be provided a new tool for exploration of human proteome.
    PROTEOMICS - CLINICAL APPLICATIONS 07/2010; 4(6-7):618-25. DOI:10.1002/prca.200900186 · 2.68 Impact Factor