1. Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis.
- Author
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Serce NB, Boesl A, Klaman I, von Serényi S, Noetzel E, Press MF, Dimmler A, Hartmann A, Sehouli J, Knuechel R, Beckmann MW, Fasching PA, and Dahl E
- Subjects
- Blotting, Western, Breast Neoplasms mortality, Breast Neoplasms pathology, Disease-Free Survival, Female, Humans, Immunohistochemistry, In Situ Hybridization, Kaplan-Meier Estimate, Prognosis, Proportional Hazards Models, RNA-Binding Proteins analysis, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tissue Array Analysis, Biomarkers, Tumor analysis, Breast Neoplasms metabolism, RNA-Binding Proteins biosynthesis
- Abstract
Background: Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level., Methods: Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression., Results: SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer., Conclusions: The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation.
- Published
- 2012
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