Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Halle (Saale), D-61120 Halle (Saale), Germany.
Int J Oncol. 2010 Apr;36(4):1015-21. doi: 10.3892/ijo_00000582.
The omicron-acyltransferase porcupine contributes to secretion and function of Wnt signaling molecules, which stimulate the expression of various cancer-related genes. Porcupine is also involved in the Wnt-induced cell signaling via beta-catenin in non-small cell lung carcinoma (NSCLC) cells. Herein, we report that the expression level of porcupine in human NSCLC tissues (n=89) positively correlates with the expression of several genes coding for cancer-related molecules such as beta-catenin, hypoxia-inducible factor-1alpha and jun B. However, the mRNA expression of porcupine was not generally increased in NSCLC compared to normal lung tissues. In NSCLC tissues we also found a positive correlation between the expression level of porcupine and the calcium-binding protein S100P, which contributes to initiation and invasion of cancer cells. Subsequent studies showed that the DNA hypomethylation with 5-aza-2'deoxycytidine increased the mRNA expression of S100P in NSCLC cells but did not alter that of porcupine. Silencing the expression of porcupine with small interfering (si)RNA reduced the expression of S100P in NSCLC cells, whereas silencing the expression of S100P with siRNA did not effect the level of Porcupine expression. In conclusion, besides DNA methylation processes, porcupine might regulate the expression of some cancer-related molecules including S100P in human NSCLC.
棘突酰基转移酶刺猬参与 Wnt 信号分子的分泌和功能,这些信号分子刺激各种与癌症相关基因的表达。刺猬还通过非小细胞肺癌 (NSCLC) 细胞中的β-连环蛋白参与 Wnt 诱导的细胞信号转导。在此,我们报告人类 NSCLC 组织(n=89)中刺猬的表达水平与编码癌症相关分子的几个基因的表达呈正相关,例如β-连环蛋白、缺氧诱导因子-1α和 jun B。然而,与正常肺组织相比,NSCLC 中刺猬的 mRNA 表达通常没有增加。在 NSCLC 组织中,我们还发现刺猬的表达水平与钙结合蛋白 S100P 之间存在正相关,S100P 有助于癌细胞的起始和浸润。随后的研究表明,5-氮杂-2'-脱氧胞苷的 DNA 低甲基化增加了 NSCLC 细胞中 S100P 的 mRNA 表达,但不改变刺猬的表达。用小干扰 (si)RNA 沉默刺猬的表达可降低 NSCLC 细胞中 S100P 的表达,而用 siRNA 沉默 S100P 的表达则不影响 Porcupine 表达水平。总之,除了 DNA 甲基化过程外,刺猬还可能调节人类 NSCLC 中包括 S100P 在内的某些与癌症相关分子的表达。