Up-regulation of S100C in normal human fibroblasts in the process of aging in vitro

Abstract S100 proteins belonging to the EF-hand Ca 2+ -binding protein family regulate a variety of cellular processes via interaction with different target proteins. Several diseases, including cancer and Alzheimer's disease, are related to a disorder of multifunctional S100 proteins, which are expressed in cell- and tissue-specific manners. We previously demonstrated that S100C could move to and accumulate in the nuclei of normal human fibroblasts but not in the nuclei of immortalized and neoplastic cells. In addition, we found that its nuclear accumulation resulted in suppression of DNA synthesis in normal cells at a confluent stage. In the present study, we investigated whether S100C was associated with cellular senescence in vitro. We found that S100C expression increased in normal human fibroblasts in the process of aging in culture and was accompanied by accumulation of its protein in the nuclei of senescent fibroblasts. In addition, the nuclear accumulation of S100C increased expression of a cyclin-dependent kinase inhibitor p21 Sdi1 , a strong inhibitor of cell growth. These findings suggest that an increase in the cells having nuclear accumulation of S100C is closely related to the process of cellular senescence of normal human fibroblasts.