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

Author:
  • Annika Jögi
  • Donal J Brennan
  • Lisa Rydén
  • Kristina Magnusson
  • Mårten Fernö
  • Olle Stål
  • Signe Borgquist
  • Mathias Uhlen
  • Göran Landberg
  • Sven Påhlman
  • Fredrik Pontén
  • Karin Jirström
Publishing year: 2009
Language: English
Pages: 1564-1574
Publication/Series: Modern Pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Volume: 22
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.Modern Pathology advance online publication, 4 September 2009; doi:10.1038/modpathol.2009.124.

Keywords

  • Cancer and Oncology
  • Surgery

Other

Published
  • CREATE Health
  • Hand Surgery, Malmö
  • Pathology, Malmö
  • Personalized Pathology & Cancer Therapy
  • ISSN: 1530-0285
Sven Påhlman
E-mail: sven.pahlman [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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