Positive Expression Of PTEN Research Articles

Correlation of cyclin D1 and cyclin D3 overexpression with the loss of PTEN expression in endometrial carcinoma

Cyclins D1 and D3 play key roles in cell cycle progression. The downregulation of cyclin D3 was associated with phosphatase and tensin homolog deleted on chromosome ten-(PTEN)-induced cell cycle arrest. We attempted to determine whether cyclin D1 and D3 overexpression is correlated with PTEN inactivation in endometrioid endometrial cancer (EEC). The expression of PTEN, cyclin D1, and cyclin D3 were determined by immunohistochemical analysis in 105 EEC specimens. Forty-three percent of the EEC demonstrated loss of PTEN expression. Cyclin D3 was overexpressed in only 18% of the EEC specimens and was not associated with tumor grade. Cyclin D1 was overexpressed in 64% of the specimens and was more common in moderate or high-grade tumors (P = 0.002 and P = 0.02, respectively). The overexpression of cyclin D3 was not correlated with loss of PTEN in the EEC. The overexpression of cyclin D1 was much higher in grade 1 tumors with negative PTEN than tumors with positive PTEN expression (67% vs 26%). The overexpression of cyclin D3 was neither frequent nor correlated with the loss of PTEN expression. The overexpression of cyclin D1 was higher in the low-grade tumors with negative PTEN expression than tumors with positive PTEN expression. Overexpression of cyclin D1 is frequent in moderate or high-grade EECs and likely results from multiple mechanisms.

NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss

We demonstrate that PTEN loss causes reduced NKX3.1 expression in both murine and human prostate cancers. Restoration of Nkx3.1 expression in vivo in Pten null epithelium leads to decreased cell proliferation, increased cell death, and prevention of tumor initiation. Whereas androgen receptor (AR) positively regulates NKX3.1 expression, NKX3.1 negatively modulates AR transcription and consequently the AR-associated signaling events. Consistent with its tumor suppressor functions, NKX3.1 engages cell cycle and cell death machinery via association with HDAC1, leading to increased p53 acetylation and half-life through MDM2-dependent mechanisms. Importantly, overexpression of Nkx3.1 has little effect on Pten wild-type epithelium, suggesting that PTEN plays a predominant role in PTEN-NKX3.1 interplay. Manipulating NKX3.1 expression may serve as a therapeutic strategy for treating PTEN-deficient prostate cancers.

Correlation between loss of PTEN expression and PKB/AKT phosphorylation in hepatocellular carcinoma

The clinical significance of phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression and the correlation between the expression of PTEN and phosphorylation of protein kinase B (PKB/AKT) in human hepatocellular carcinoma (HCC) were investigated. The expression of PTEN and phospho-AKT was detected by SP immunohistochemical technique and Western blotting in 35 cases of HCC, 15 cases of liver cirrhosis and 8 cases of normal tissues. The correlation between the expression of PTEN and PKB/AKT in HCC was analyzed. The results showed that the positive expression of PTEN in HCC (62.9%, 0.085 +/- 0.021) was significantly lower than that in liver cirrhosis and normal tissues (P < 0. 01). The expression level of PTEN was related to the differentiation degree of HCC and the status of metastasis (P < 0.05). Western blotting revealed a significant inverse correlation between PTEN and phospho-AKT (r = -0.818, P < 0.01). These results demonstrated that down-regulation or loss of PTEN, which may not be able to effectively inhibit the hyper-phosphorylation of PKB/AKT, might play an important role in tumorigenesis and progression of HCC.

Expression of E-Cadherin and the PTEN gene in relation to invasion and metastasis of gastric carcinomas

OBJECTIVE To observe the expression of PTEN and E-Cadherin in gastric carcinomas (GCs), and to investigate the relationship between their expression and the pathology and prognosis of patients with GC. METHODS The proposed markers were detected inmmunohistochemically by using the SABC method in 100 post-operated specimens of GC, The results were statically analyzed by the chi-square and log rank tests, RESULTS Both E-Cadherin and PTEN proteins were expressed in non-cancerous mucosa. They were reduced or lost in GCs. The abnormal rate of expression of E-Cadherin was 42.0%. The decreased rate of expression in the diffuse-type GC 48,6%) was significantly higher than in the intestinal- type GC (26.7%, P <0.05). The abnormal expression of E-Cadherin closely correlated tothe depth of invasion ( P <0.05). The degree ol loss of the PTEN protein was 59.0% in GCs. In the diffuse-type GC, the rate of loss of PTEN was (65.7%) which was significantly higher than that in the intestinal-type GC (43.3%, P <0.05). The rate of loss of PTEN (64.5%) in GCs with lymph node metastasis was significantly higher than that in GCs without metastasis (41.7%, P <0.05). The prognosis of patients with a loss of PTEN protein was worse than the patients with positive expression of PTEN ( P =0.0066)~ E- Cadherin was normally expressed in 65.9% of GCs with positive expression of PTEN. CONCLUSION The toss of E-Cadherin and PTEN markers correlated with infusion and metastasis of GC. The expression of PTEN showed a close relationship to the prognosis of patients. Detection of the 2 markers together aided in the correct prediction of the prognosis of the GC patients and provided information for clinical treatment.

Complications, continence and quality of life after an intensive preoperative radio-chemotherapy regimen for locally advanced rectal cancer: analysis of a phase I–II study

Complications, continence and quality of life after an intensive preoperative radio-chemotherapy regimen for locally advanced rectal cancer: analysis of a phase I–II study

Loss of PTEN expression as a prognostic marker for tongue cancer.

Abnormalities of PTEN, a candidate tumor suppressor gene located at 10q23.3, play an important role in the tumorigenesis of multiple tumor types. To investigate the expression of PTEN and its clinical implication in squamous cell carcinoma of the tongue. Retrospective analysis of PTEN protein expression in archived primary oral tongue tumor samples. Academic center. PTEN expression was determined by immunohistochemical analysis in tissue samples from 41 patients with stage II, III, and IV squamous cell carcinoma of the tongue. All the patients underwent curative surgical treatment with a median follow-up of 81 months. The Kaplan-Meier method was used for survival analysis. Multivariate analysis was performed according to the Cox proportional hazards model. Lack of staining for PTEN was demonstrated in 12 (29%) of the 41 tumors. Patients whose tumors lacked PTEN expression had a significantly shorter overall survival time (P = .03) and event-free survival time (P = .01) than those patients with positive PTEN expression. Multivariate regression analysis demonstrated that PTEN expression is an independent predictor of poor outcome when compared with tumor stage and nodal status. Although genetic alterations of the PTEN gene are rare in head and neck squamous cell carcinoma, loss of PTEN is not an uncommon event in squamous cell carcinoma of the tongue. Lack of PTEN expression may be an independent prognostic indicator for clinical outcome in patients with this tumor type.