Clinical Translational Division, Translational Genomics Research Institute, Scottsdale, Arizona, United States of America.
PLoS One. 2012;7(3):e32783. doi: 10.1371/journal.pone.0032783. Epub 2012 Mar 1.
The Hippo pathway regulates organ size by inhibiting cell proliferation and promoting cell apoptosis upon its activation. The Yes Associated Protein 1 (YAP1) is a nuclear effector of the Hippo pathway that promotes cell growth as a transcription co-activator. In human cancer, the YAP1 gene was reported as amplified and over-expressed in several tumor types.
Immunohistochemical staining of YAP1 protein was used to assess the expression of YAP1 in pancreatic tumor tissues. siRNA oligonucleotides were used to knockdown the expression of YAP1 and their effects on pancreatic cancer cells were investigated using cell proliferation, apoptosis, and anchorage-independent growth assays. The Wilcoxon signed-rank, Pearson correlation coefficient, Kendall's Tau, Spearman's Rho, and an independent two-sample t (two-tailed) test were used to determine the statistical significance of the data.
Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining intensities were moderate to strong in the nucleus and cytoplasm of the tumor cells, whereas the adjacent normal epithelial showed negative to weak staining. In cultured cells, YAP1 expression and localization was modulated by cell density. YAP1 total protein expression increased in the nuclear fractions in BxPC-3 and PANC-1, while it declined in HPDE6 as cell density increased. Additionally, treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting siRNA oligonucleotides significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA oligonucleotides diminished the anchorage-independent growth on soft agar of pancreatic cancer cells, suggesting a role of YAP1 in pancreatic cancer tumorigenesis.
YAP1 is overexpressed in pancreatic cancer tissues and potentially plays an important role in the clonogenicity and growth of pancreatic cancer cells.
Hippo 通路通过在其激活时抑制细胞增殖和促进细胞凋亡来调节器官大小。Yes 相关蛋白 1（YAP1）是 Hippo 通路的核效应物，作为转录共激活因子促进细胞生长。在人类癌症中，YAP1 基因在几种肿瘤类型中被报道扩增和过度表达。
使用 YAP1 蛋白的免疫组织化学染色来评估胰腺肿瘤组织中 YAP1 的表达。使用 siRNA 寡核苷酸敲低 YAP1 的表达，并使用细胞增殖、凋亡和非锚定依赖性生长测定来研究其对胰腺癌细胞的影响。Wilcoxon 符号秩检验、Pearson 相关系数、Kendall's Tau、Spearman's Rho 和独立的两样本 t（双侧）检验用于确定数据的统计学意义。
在胰腺肿瘤组织的免疫组织化学研究中，YAP1 染色强度在肿瘤细胞的核和细胞质中为中度至强，而相邻的正常上皮呈阴性至弱染色。在培养的细胞中，YAP1 的表达和定位受细胞密度的调节。在 BxPC-3 和 PANC-1 中，YAP1 总蛋白表达在核部分增加，而随着细胞密度的增加，HPDE6 中的表达下降。此外，用 YAP1 靶向 siRNA 寡核苷酸处理胰腺癌细胞系 BxPC-3 和 PANC-1，显著减少了它们在体外的增殖。此外，YAP1 siRNA 寡核苷酸处理减少了胰腺癌细胞在软琼脂上的非锚定依赖性生长，表明 YAP1 在胰腺癌细胞肿瘤发生中起作用。
YAP1 在胰腺癌细胞中过度表达，并且可能在胰腺癌细胞的集落形成和生长中发挥重要作用。
