Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
J Surg Oncol. 2011 Nov 1;104(6):679-84. doi: 10.1002/jso.22004. Epub 2011 Jun 21.
Wip1 over-expression inhibits p53 function and reduces selection for TP53 mutations during cancer progression. To clarify the correlation of Wip1 with TP53/p14(ARF) pathway disruption in astyrocytomas, the expression of Wip1 and TP53/p14(ARF) pathway alterations have been investigated.
Tumor samples of 52 patients of astrocytomas were examined for TP53 mutations, p14(ARF) expression, and Wip1 expression. Direct sequencing of region from exons 5 to 8 of the TP53 gene was performed on the genomic DNA in each sample. The DNA methylation states of the CpG islands of the p14(ARF) gene were determined by MSP. The expression of Wip1 was analyzed by real-time quantitative PCR, Western blot, and immunohistochemical staining.
Disruption of the TP53/p14ARF pathway was detected in 57.7% of samples. Among 22 cases without TP53 and p14ARF alterations, 11 (50%) had Wip1 mRNA over-expression. In tumors with wild-type TP53 and p14ARF, Wip1 mRNA was over-expressed only 1 case out of 30 (3.3%). Higher levels of Wip1 were associated with TP53 mutations but not with lower levels of expression of p14(ARF) or aberrant promoter hypermethylation of the p14(ARF) gene.
Wip1 is selectively over-expressed in astyrocytomas without alterations in TP53 or p14(ARF). Wip1 may inhibit the TP53/p14(ARF) pathway.
Wip1 过表达抑制 p53 功能，并减少癌症进展过程中 TP53 突变的选择。为了阐明 Wip1 与星形细胞瘤中 TP53/p14(ARF) 通路失活的相关性，研究了 Wip1 和 TP53/p14(ARF) 通路改变的表达。
对 52 例星形细胞瘤患者的肿瘤样本进行了 TP53 突变、p14(ARF) 表达和 Wip1 表达检测。对每个样本的基因组 DNA 进行了 TP53 基因外显子 5 到 8 区的直接测序。通过 MSP 确定了 p14(ARF) 基因 CpG 岛的 DNA 甲基化状态。通过实时定量 PCR、Western blot 和免疫组织化学染色分析了 Wip1 的表达。
检测到 57.7%的样本中存在 TP53/p14ARF 通路失活。在没有 TP53 和 p14ARF 改变的 22 例病例中，有 11 例（50%）Wip1 mRNA 过表达。在野生型 TP53 和 p14ARF 的肿瘤中，仅在 30 例中的 1 例（3.3%）中观察到 Wip1 mRNA 过表达。较高水平的 Wip1 与 TP53 突变相关，但与 p14(ARF)表达水平降低或 p14(ARF) 基因启动子异常高甲基化无关。
Wip1 在没有 TP53 或 p14(ARF)改变的星形细胞瘤中选择性过表达。Wip1 可能抑制 TP53/p14(ARF)通路。
