Watanabe S, Uchida T
Department of Oncology, Nippon Roche Research Center, Kamakura, Japan.
Biochim Biophys Acta. 1996 Jun 13;1312(2):99-104. doi: 10.1016/0167-4889(96)00024-9.
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 1 alpha,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 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.
我们发现，维生素D3可上调某些人类实体瘤细胞系以及单核细胞白血病细胞系中胞苷脱氨酶（CDD）基因的表达。从人胎盘中鉴定出两种全长CDD cDNA：一种在密码子27处含有谷氨酰胺，另一种含有赖氨酸。在各种正常组织和癌细胞系中检测了其表达。Northern印迹分析表明，白细胞中CDD mRNA水平较高，而在肝脏、肾脏、胎盘、脾脏和肺中水平中等。CDD在20种人类癌细胞系中的表达高度可变，且与其在正常组织中的表达无关。用1α,25 - 二羟基维生素D3处理细胞系，导致某些细胞系中CDD表达上调，而其他细胞系则未上调。在用维生素D3处理24小时后，五个胃癌细胞系中的三个和八个结肠癌细胞系中的五个CDD mRNA水平升高。在用维生素D3处理3小时后，在胃癌MKN 45细胞中检测到mRNA增加，并在24至48小时后测量到酶活性增加。但未发现骨化三醇与9 - 顺式视黄酸的联合作用。我们的结果表明，在某些实体瘤细胞系中，维生素D3可上调CDD的表达。
