Evaluation of claspin as a proliferation marker in human cancer and normal tissues.

Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Greece.
The Journal of Pathology (Impact Factor: 7.43). 02/2007; 211(3):331-9. DOI: 10.1002/path.2095
Source: PubMed

ABSTRACT 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.

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Available from: Petros Tsantoulis, Aug 03, 2014
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    • "Claspin plays a poorly understood, positive role in DNA replication, which appears distinct from its role in checkpoint signaling. In fact, not only does expression of Claspin represent a reliable marker of cell proliferation in both human cancer and normal tissues (Tsimaratou et al., 2007), but Claspin overexpression has also been shown to increase cell proliferation (Lin et al., 2004). Our finding suggests that Claspin represents another substrate that APC/C Cdh1 keeps at low levels during G1 to avoid premature entry into S. "
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