Evaluation of claspin as a proliferation marker in human cancer and normal tissues
Autor: | Dimitris Kletsas, I Poulias, Monica Venere, Maria Sideridou, N.G. Kastrinakis, V G Gorgoulis, M Salmas, Thanos D. Halazonetis, Ch. Kittas, Katerina Tsimaratou, Kostas Evangelou, Michalis Liontos, Petros Tsantoulis |
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Rok vydání: | 2006 |
Předmět: |
DNA Replication
Pathology medicine.medical_specialty Lung Neoplasms DNA Repair DNA damage Cyclin A Blotting Western Statistics Nonparametric Pathology and Forensic Medicine Cell Line S Phase Neoplasms medicine Biomarkers Tumor Humans Proliferation Marker Nuclear protein Cell synchronization Fluorescent Antibody Technique Indirect Adaptor Proteins Signal Transducing Cell Proliferation Osteosarcoma biology Cell growth Carcinoma Antibodies Monoclonal Cell cycle Fibroblasts Molecular biology Immunohistochemistry Ki-67 Antigen Case-Control Studies biology.protein Colorectal Neoplasms |
Zdroj: | The Journal of pathology. 211(3) |
ISSN: | 0022-3417 |
Popis: | Claspin is a nuclear protein involved in DNA replication and the DNA damage response. Its structural and functional properties suggest that it may represent a potentially useful proliferation marker. To this end, a monoclonal antibody was generated and the expression of claspin was investigated in normal fibroblasts and various cancer cell lines, as well as in tumour and normal tissues from patients with primary epithelial carcinomas. Immunoblotting analysis confirmed the specificity of the antibody, while immunohistochemistry demonstrated its applicability in archival material. In normal cells and tissues, claspin expression was weak, whereas increased levels were observed in cancer cell lines and tumour specimens. Claspin staining correlated strongly with Ki67 staining in both normal (p < 0.001) and tumour tissues (p < 0.001). However, the labelling index (LI) of claspin was consistently lower than that of Ki67, suggesting that claspin expression may be limited to a narrower part of the cell cycle. Co-localization assays with cyclin A and cell synchronization experiments indicated that claspin expression coincides with the S phase. Interestingly, the relative increase of the claspin LI in tumour samples compared with normal tissues was significantly higher (14-fold) than that of the Ki67 LI (five-fold), suggesting that claspin may be a more sensitive marker of aberrant proliferation. |
Databáze: | OpenAIRE |
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