14-3-3sigma is down-regulated in human prostate cancer.
14-3-3sigma is down-regulated in human prostate cancer.
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DOI：
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发表时间：
2004
影响因子：
3.1
通讯作者：
T. Urano;Satoru Takahashi;Takashi Suzuki;T. Fujimura;M. Fujita;J. Kumagai;Kuniko Horie-Inoue;H. Sasano;T. Kitamura;Y. Ouchi;S. Inoue
中科院分区：
文献类型：
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作者：
T. Urano;Satoru Takahashi;Takashi Suzuki;T. Fujimura;M. Fujita;J. Kumagai;Kuniko Horie-Inoue;H. Sasano;T. Kitamura;Y. Ouchi;S. Inoue
14-3-3sigma是细胞周期的负调节因子，由p53在DNA损伤时诱导。它被认为是一种上皮特异性标记物，在乳腺癌中发现了该蛋白的下调，这表明它在上皮细胞中具有肿瘤抑制活性。本研究表明，与正常前列腺上皮细胞相比，14-3-3sigma蛋白在人前列腺癌细胞系、LNCaP、PC3和DU145中下调。原代前列腺细胞免疫组化分析显示14-3-3 - sigma蛋白的表达是上皮细胞特异性的。前列腺病理标本中，95%的良性增生标本细胞质中可见明显的弥漫性14-3-3 - sigma免疫染色，而癌标本中阳性率< 20%。在前列腺癌细胞中14-3-3sigma下调的机制方面，基因启动子的高甲基化在LNCaP细胞中起因果作用，5-aza-2'-脱氧胞苷去甲基化处理使14-3-3sigma mRNA水平升高。有趣的是，蛋白酶体介导的蛋白水解是DU145和PC3细胞中14-3-3sigma减少的原因，因为用蛋白酶体抑制剂MG132处理后，14-3-3sigma蛋白表达增加。此外，肿瘤坏死因子相关的凋亡诱导配体在DU145和PC3细胞中增强14-3-3sigma基因和蛋白的表达。这些数据表明，在前列腺上皮细胞的肿瘤转化过程中，14-3-3 - sigma的表达下调。
The 14-3-3sigma is a negative regulator of the cell cycle, which is induced by p53 in response to DNA damage. It has been characterized as an epithelium-specific marker and down-regulation of the protein has been shown in breast cancers, suggesting its tumor-suppressive activity in epithelial cells. Here we demonstrate that 14-3-3sigma protein is down-regulated in human prostate cancer cell lines, LNCaP, PC3, and DU145 compared with normal prostate epithelial cells. Immunohistochemical analysis of primary prostate cells shows that the expression of 14-3-3sigma protein is epithelial cell-specific. Among prostate pathological specimens, > 95% of benign hyperplasia samples show significant and diffuse immunostaining of 14-3-3sigma in the cytoplasm whereas < 20% of carcinoma samples show positive staining. In terms of mechanisms for the down-regulation of 14-3-3sigma in prostate cancer cells, hypermethylation of the gene promoter plays a causal role in LNCaP cells as 14-3-3sigma mRNA level was elevated by 5-aza-2'-deoxycytidine demethylating treatment. Intriguingly, the proteasome-mediated proteolysis is responsible for 14-3-3sigma reduction in DU145 and PC3 cells, as 14-3-3sigma protein expression was increased by treatment with a proteasome inhibitor MG132. Furthermore, tumor necrosis factor-related apoptosis-inducing ligand enhances 14-3-3sigma gene and protein expression in DU145 and PC3 cells. These data suggest that 14-3-3sigma expression is down-regulated during the neoplastic transition of prostate epithelial cells.