Expression of cytidine deaminase in human solid tumors and its regulation by 1 α,25-dihydroxyvitamin D₃

We found that vitamin D₃ up-regulates the expression of cytidine deaminase (CDD) gene in some human solid tumor cell lines as well as the monocytic leukemia cell lines. Two kinds of full length CDD cDNA were identified from human placenta: one has glutamine and the other one has lysine at codon 27. The expression was tested in various normal tissues and the cancer cell lines. Northern blot analysis demonstrated high levels of CDD mRNA in leukocytes and moderate levels in liver, kidney, placenta, spleen and lung. Expression of CDD in 20 human cancer cell lines was highly variable and not related to its expression in normal tissues. Treatment of the cell lines with 1α,25-dihydroxyvitamin D₃ resulted in up-regulation of CDD expression in some lines but not others. Three of five gastric carcinoma cell lines and five of eight colorectal cancer cell lines had increased levels of CDD mRNA following 24 h treatment with vitamin D₃. Increased mRNA was detected in gastric cancer MKN 45 cells after 3 h of treatment with vitamin D₃ and increased enzyme activity was measured after 24 to 48 h. But no combined effect of calcitriol with 9-cis retinoic acid was found. Our results demonstrate that CDD can be up-regulated by vitamin D₃ in some solid tumor cell lines.