DOWN-REGULATION OF A MEMBER OF THE S100 GENE FAMILY IN MAMMARY-CARCINOMA CELLS AND REEXPRESSION BY AZADEOXYCYTIDINE TREATMENT
DOWN-REGULATION OF A MEMBER OF THE S100 GENE FAMILY IN MAMMARY-CARCINOMA CELLS AND REEXPRESSION BY AZADEOXYCYTIDINE TREATMENT
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DOI：
10.1073/pnas.89.6.2504
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发表时间：
1992-03-15
影响因子：
11.1
通讯作者：
SAGER, R
中科院分区：
文献类型：
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作者：
LEE, SW;TOMASETTO, C;SAGER, R
一个cDNA克隆，命名为CaN19（最初称为克隆19），通过减法杂交分离，包含优先表达在正常乳腺上皮细胞而不是乳腺肿瘤细胞的序列。将其推断的氨基酸序列与GenBank数据库中的序列进行比较，发现与S100蛋白家族相似，S100蛋白家族是一组参与细胞周期进程和细胞分化的Ca2+结合调节蛋白。在正常细胞中，钙离子载体A23187下调CaN19的表达，表明其调控是钙依赖的。我们将CaNl9定位到人类染色体1q21-q24上，该区域包含另外四个s100相关基因。与CaN19 mRNA的表达相反，S100蛋白家族的大多数成员在肿瘤细胞中被激活或过表达。生长因子剥夺同步实验表明，正常细胞中CaN19的表达呈双相诱导，在G1期早期几乎等于2倍，在G1/S边界另一个2- 3倍。将乳腺肿瘤细胞暴露于5-aza-2'-脱氧胞苷（一种DNA甲基化抑制剂）中，可以重新激活CaN19 mRNA的表达。
A cDNA clone, designated CaN19 (originally called clone 19), isolated by subtractive hybridization, contains sequences that are preferentially expressed in normal mammary epithelial cells but not in breast tumor cells. Comparison of its deduced amino acid sequence with sequences in the GenBank data base revealed similarity with the S100 protein family, a group of small Ca2+-binding modulator proteins involved in cell cycle progression and cell differentiation. CaN19 expression is down-regulated in normal cells by A23187, a calcium ionophore, suggesting that its regulation is calcium-dependent. We have assigned CaNl9 to human chromosome 1q21-q24, a region containing four other S100-related genes. In contrast to CaN19 mRNA expression, most members of the S100 protein family are activated or overexpressed in tumor cells. Synchronization experiments by growth-factor deprivation demonstrated a biphasic induction of CaN19 expression in normal cells, almost-equal-to 2-fold in early G1 phase and another 2- to 3-fold at the G1/S boundary. Exposure of mammary tumor cells to 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, reactivated the expression of CaN19 mRNA.