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Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells.

ABSTRACT: BACKGROUND:Hepatocellular carcinoma (HCC) is a lethal malignancy with high rate of metastasis and poor prognosis. There are no effective managements to block metastasis of HCC. Programmed cell death 4 (PDCD4) is found to be a tumor transformation suppressor. Among investigations on effects of PDCD4, little is about the metastatic potentials of HCC cells. This study was to investigate the role of PDCD4 on metastatic potential of human HCC cells. METHODS:We examined the expression of PDCD4 in three HCC cell lines with different metastatic potentials, MHCC-97H (high metastatic potential), MHCC-97L (low metastatic potential) and Hep3B (no metastatic potential). A plasmid encoding PDCD4 gene was constructed and then transfected into HCC cells with the lowest PDCD4 expression level. Effects of PDCD4 on cell proliferation, cell apoptosis, gene expression of metastasis tumor antigen 1 (MTA1) and in vitro migration and invasion capacity were assessed after transfection. RESULTS:Our results showed that the expression level of PDCD4 was inversely correlated to the metastatic potential of HCC cells. After transfection with the PDCD4 gene, HCC cell proliferation rate was significantly decreased, cell apoptosis rate was significantly increased, the expression of MTA1 gene, HCC cell migration and Matrigel invasion were also remarkably inhibited. CONCLUSION:PDCD4 expression is inversely correlated to the metastatic potential of HCC cells. PDCD4 can effectively suppress the metastatic potential of HCC cells.

SUBMITTER: Zhang S

PROVIDER: S-EPMC2705348 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells.

Zhang Shuhong S Li Jianfeng J Jiang Ying Y Xu Yijun Y Qin Chengyong C

Journal of experimental & clinical cancer research : CR 20090529

<h4>Background</h4>Hepatocellular carcinoma (HCC) is a lethal malignancy with high rate of metastasis and poor prognosis. There are no effective managements to block metastasis of HCC. Programmed cell death 4 (PDCD4) is found to be a tumor transformation suppressor. Among investigations on effects of PDCD4, little is about the metastatic potentials of HCC cells. This study was to investigate the role of PDCD4 on metastatic potential of human HCC cells.<h4>Methods</h4>We examined the expression o ...[more]

PMID: 19480673

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Project description:Background:The primary goal of papillary thyroid cancer (PTC) management was to stratify patients at pre- and post-surgical level to identify the small proportion of cases with potentially aggressive disease. Purpose:The aim of our study is to evaluate the possible role of programmed cell death 4 (PDCD4) and BRAF status as prognostic markers in PTC. Patients and methods:We investigate programmed cell death 4 (PDCD4) immunohistochemical expression in 125 consecutive PTCs with median follow-up of 75.3 months (range, 15-98 months) to verify the possible correlation between BRAF status and correlate the classical clinicopathological prognostic factors and PTC outcome with PDCD4 expression. To further support the data, miR-21 expression was tested (by quantitative real-time PCR and in situ hybridization) in a different series of 30 cases (15 PTCs BRAFwt and 15 PTCs BRAFV600E). Moreover, we validated our results using TGCA thyroid carcinoma dataset. Results:We found that 59.8% of the patients showed low-grade PDCD4 nuclear expression and low-grade expression correlated with BRAF V600E. Compared with BRAF 15 wild-type tissue samples, a significant miR-21 up-regulation was associated with BRAF V600E mutations. Low-grade PDCD4 resulted, and was associated with aggressive histological variants, higher cancer size, extra-thyroidal extension, multifocality, lymph-node metastasis and lymph nodal ratio at the diagnosis. Concerning the outcome, the low-grade PDCD4 expression correlated at univariate and multivariate analysis, with lower levels of recurrence-free survival rate (RFS) and with poor outcome. Moreover, there was significant association between BRAF V600E patients with PDCD4 nuclear loss and lower RFS, whilet here was significant association between BRAF wild-type patients with PDCD4 nuclear expression and better outcome. Conclusion:These results showed that PDCD4 could predict PTC outcome and that the sum of PDCD4 and BRAF alterations increases the prognostic power of BRAF mutation alone.

Dataset Information

Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells.

Publications

Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells.

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