B11
GINS proteins as candidate markers for cancer diagnosis
Nina Marinsek1, Anthony Mills1, Cinzia G Scarpini1, Emily Ikelle1, Richard Miller4, David Neal3, Nicholas Coleman1, Stephen D Bell2, Ronald Laskey1
1MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK, 2Sir William Dunn School of Pathology, Oxford University, Oxford, UK, 3Cancer Research UK Cambridge Research Institute, Cambridge, UK, 4Department of Surgery, Addenbrooke's NHS Trust, Cambridge, UK
The GINS complex (a heterotetramer of Sld5, Psf1, Psf2 and Psf3) is a highly conserved DNA replication factor required for both the initiation of chromosome replication and the progression of replication forks. GINS interacts with the MCM complex in eukaryotes and archaea. Given the value of MCM proteins as specific and sensitive markers for cancer screening, we investigated whether GINS subunits might also have potential diagnostic value. Consistent with the published findings for MCM, GINS proteins are expressed in all cycle phases of cultured proliferating cells, but are down-regulated in cells undergoing differentiation or quiescence.
Examination of histological sections indicates that Sld5 and Psf3 expression is restricted to the proliferative compartment in normal tissue but spreads to the majority of cells in a wide range of dysplastic and malignant tissues, including cervix, colon and skin. Preliminary findings suggest that Sld5 may be more stable than Mcm2 in certain extracellular environments such as urine and faeces. We therefore present an evaluation of Sld5 as a potential biomarker in urine samples from prostate cancer patients and colonocytes from colon cancer patients. Work is ongoing to determine further applications of GINS in cancer screening and prognosis. We are also investigating the intracellular distribution and functions of GINS.
