Increased pontin expression in human colorectal cancer tissue.
ABSTRACT Wnt signaling plays a fundamental role in the control of cell proliferation and differentiation and is frequently deregulated in colorectal carcinoma leading to an enhanced expression of Wnt target genes. Pontin, a member of the AAA(+) superfamily, has previously been shown to interact with beta-catenin and to enhance TCF/beta-catenin-mediated transcription of Wnt target genes and thus may contribute to carcinogenesis. Here, we studied the expression of pontin in 34 patients with histologically proven colorectal cancer by immunohistochemistry on paraffin-embedded colorectal cancer samples using the monoclonal mouse anti-pontin (5G3-11) antibody. Cytoplasmic pontin staining of tumor cells was present in all cases and was stronger in 84.6% and equal in 15.4% of the cases compared with normal mucosa. In 50% of tumor specimens, an additional nuclear pontin staining pattern was noted with positivity ranging from 10% to 60% of the nuclei. Interestingly, all cases with nuclear pontin expression also revealed nuclear beta-catenin localization. Furthermore, pontin staining was stronger at the invasive margin and in tumor buds than in the tumor center in 41.2% and 37.9% of the cases, respectively. In this context, 66.7% and 64.7% of the cases with enhanced beta-catenin staining at the invasive margin and in tumor buds, respectively, also revealed stronger pontin expression. Analysis of pontin expression in 8 patients by Western blotting confirmed the histologic results. These data suggest that upregulation and nuclear localization of pontin together with beta-catenin may contribute to progression of colorectal carcinoma.
SourceAvailable from: Chun-Wei Tung[Show abstract] [Hide abstract]
ABSTRACT: Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.The Scientific World Journal 12/2013; 2013:782031. DOI:10.1155/2013/782031 · 1.73 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. Distant metastasis represents the major cause of death in patients with RCC. Recent studies have implicated the AAA+ ATPase pontin in many cellular activities that are highly relevant to carcinogenesis. In this study, we demonstrate for the first time that pontin was up-regulated in RCC, and plays a previously unknown pro-invasive role in the metastatic progression of RCC through epithelial-to-mesenchymal transition (EMT) pathway. 28 pairs of freshly frozen clear cell RCC samples and the matched normal renal tissues analyzed by quantitative RT-PCR and western blotting demonstrated that pontin was up-regulated in clear cell RCC tissues than in normal renal tissues. In addition, immunohistochemistry was used to evaluate subcellular pontin expression in 95 RCC patients, and found that overexpression of pontin in cytoplasm positively correlated with the metastatic features, predicting unfavorable outcomes of RCC patients. Furthermore, in vitro experiments show pontin was predominantly expressed in cytoplasm of RCC cell lines, and a significant suppression of cell migration and invasion in pontin siRNA treated RCC cell lines was observed. Mechanistic studies show that pontin depletion up-regulated the E-cadherin protein and down-regulated vimentin protein, and decreased nuclear β-catenin expression, suggesting the involvement of EMT in pontin induced metastatic progression. Together, our data suggest pontin as a potential prognostic biomarker in RCC, and provide new promising therapeutic targets for clinical intervention of kidney cancers.PLoS ONE 03/2015; 10(3):e0118659. DOI:10.1371/journal.pone.0118659 · 3.53 Impact Factor
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ABSTRACT: In recent years, tumor budding in colorectal cancer has gained much attention as an indicator of lymph node metastasis, distant metastatic disease, local recurrence, worse overall and disease-free survival, and as an independent prognostic factor. Tumor buds, defined as the presence of single tumor cells or small clusters of up to five tumor cells at the peritumoral invasive front (peritumoral buds) or within the main tumor body (intratumoral buds), are thought to represent the morphological correlate of cancer cells having undergone epithelial-mesenchymal transition (EMT), an important mechanism for the progression of epithelial cancers. In contrast to their undisputed prognostic power and potential to influence clinical management, our current understanding of the biological background of tumor buds is less established. Most studies examining tumor buds have attempted to recapitulate findings of mechanistic EMT studies using immunohistochemical markers. The aim of this review is to provide a comprehensive summary of studies examining protein expression profiles of tumor buds and to illustrate the molecular pathways and crosstalk involved in their formation and maintenance.03/2015; 2:11. DOI:10.3389/fmed.2015.00011