Over-expression of wild-type p53-induced phosphatase 1 confers poor prognosis of patients with gliomas.
ABSTRACT Wild-type p53-induced phosphatase 1 (Wip1) is a member of the protein phosphatase 2C family, which is characterized by distinctive oncogenic properties. Overexpression of Wip1 is observed in certain types of human tumors that are associated with significantly poor prognosis. This study aimed to detect the expression of Wip1 in gliomas and to analyze its prognostic value in the patients. Wip1 mRNA and protein expression profiles in 81 gliomas and 15 normal brain tissues were detected using RT-PCR, Western blot and immunohistochemistry. The specimens were stained with proliferating cell nuclear antigen (PCNA) and p53 and evaluated using immunohistochemistry. Detailed clinical and demographic information of patients were retrospectively collected until 5years post-operation. Kaplan-Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. Wip1-positive expression was observed in the majority of glioma tissues, whereas no Wip1 expression was detected in the normal brain tissues. Wip1-positive expression significantly correlated with glioma histological grade. The PCNA index was higher in the Wip1-positive group compared to that in the Wip1-negative group. A univariate analysis and log-rank test indicated that statistically significant association between Wip1 expression and the lower overall survival rate in the patients with glioma. A multivariate analysis also indicated a statistically significant association between increased Wip1 expression and lower overall survival rate. Our results suggest that Wip1 may be related to pathological diagnosis and prognosis evaluation for malignant gliomas.
- SourceAvailable from: René H Medema[Show abstract] [Hide abstract]
ABSTRACT: The DNA damage response (DDR) pathway and its core component tumor suppressor p53 block cell cycle progression after genotoxic stress and represent an intrinsic barrier preventing cancer development. The serine/threonine phosphatase PPM1D/Wip1 inactivates p53 and promotes termination of the DDR pathway. Wip1 has been suggested to act as an oncogene in a subset of tumors that retain wild-type p53. In this paper, we have identified novel gain-of-function mutations in exon 6 of PPM1D that result in expression of C-terminally truncated Wip1. Remarkably, mutations in PPM1D are present not only in the tumors but also in other tissues of breast and colorectal cancer patients, indicating that they arise early in development or affect the germline. We show that mutations in PPM1D affect the DDR pathway and propose that they could predispose to cancer.The Journal of Cell Biology 05/2013; · 9.69 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Wild-type p53-induced phosphatase (WIP1) is overexpressed and functionally altered in multiple human malignancies. The present study investigated its abnormal expression and dysfunctions in nasopharyngeal carcinoma (NPC) in vitro. Here, analysis of WIP1 mRNA and protein in human NPC tissues revealed that both WIP1 messenger RNA (mRNA) and protein were elevated and were correlated with NPC clinical stage and metastasis in patients. In vitro experiments further showed that WIP1 inhibition led to a decrease in the proliferative ability of NPC CNE-2 and 5-8F cells accompanied by cell cycle arrest and increased apoptosis. In addition, WIP1 knockdown inhibited the invasiveness of CNE-2 and 5-8F cells and was associated with the down-regulation of the expression of matrix metallopeptidase 9 (MMP-9) mRNA and protein. Taken together, our data demonstrate that WIP1 regulates the proliferation and invasiveness of NPC cells in vitro, and this may be correlated with its modulation of MMP-9 expression, cell cycle progression and apoptosis. WIP1 functioned as a potential therapeutic target in NPC management.Tumor Biology 05/2014; · 2.84 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Aim: To investigate the level of expression of proto-oncogene Wip1 and its physiological significance in colorectal cancer. Methods: Immunohistochemistry, semi-quantitative RT-PCR, and Western blotting were used to analyze Wip1 mRNA and protein expression in 120 cases of colorectal cancer and normal tissues to study relationships with clinical symptoms and disease prognosis. Results: The level of Wip1 protein expression was found to be significantly higher in colorectal cancer tissues (85% (102/120)) than in normal tissues (30% (36/120)) (P < 0.05). The relative amount of Wip1 protein in colorectal cancer tissue was also found to be significantly higher (P < 0.05) than in normal tissues (1.060±0.02 and 0.640±0.023, respectively). Semi-quantitative RT-PCR showed average Wip1 mRNA expression levels to be 1.113 ±0.018 and 0.658±0.036 for colorectal cancer tissue and adjacent normal tissue (P < 0.05). The level of Wip1 protein expression was not correlated with age, gender, or tumor site, but appeared linked with lymph node metastasis, Dukes stage, histological grade, and liver metastasis. Individuals with high and low levels of Wip1 expression showed statistically significant differences in the five-year overall survival and recurrence-free survival rates (P < 0.05). Conclusion: Wip1 mRNA and protein are highly expressed in colorectal cancers and may be associated with colorectal cancer development and progression.Asian Pacific journal of cancer prevention: APJCP 03/2013; 14(3):1975-9. · 1.50 Impact Factor