S100A2 is a member of the subfamily of S100 Ca2+-binding proteins, characterized by two distinct EF-hand structural motifs. It is a homodimeric protein that upon binding of calcium undergoes a conformational change. The S100A2 protein has been first detected in lung and kidney and is mainly expressed in a subset of tissues and cells such as breast epithelia and liver. Interestingly the cDNA coding for the S100A2 protein was identified as a novel tumor suppressor gene by subtractive hybridization between normal and tumorderived human mammary epithelial cells. Expression studies showed that the S100A2 gene is markedly down-regulated in several tumor tissues of various origins like melanomas (13) and breast carcinoma (14). Moreover, growth factors were reported to alter the S100A2 gene expression at late G1/S-phase, indicating that S100A2 is cell cycle-regulated. Site-specific DNA methylation of the S100A2 gene promoter region in normal versus tumorigenic breast cancer cell lines indicated repression of gene expression in tumor cells, thus suggesting a role for S100A2 in suppression of tumor cell growth and possibly inhibition of tumor progression.