Increased pontin expression in human colorectal cancer tissue

Department of General, Vascular and Thoracic Surgery, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Human Pathlogy (Impact Factor: 2.77). 08/2007; 38(7):978-85. DOI: 10.1016/j.humpath.2007.01.005
Source: PubMed


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.

6 Reads
  • Source
    • "RUVBL1 is reported to regulate COX-2 gene expression that plays a crucial role in the progress and transformation of colon cancer [33]. Overexpression of RUVBL1 was also reported in hepatocellular carcinoma [34, 35], colorectal tumor [36], nonsmall cell lung cancer [37], B-cell lymphoma [38], and breast cancer [39]. Two SNPs in RUVBL1 were found to be associated with increased risk of serous ovarian cancer [40]. "
    [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.
    Full-text · Article · Dec 2013 · The Scientific World Journal
  • Source
    • "The knockout of scRuvBL1 demonstrated that it is essential for the survival of yeast [15]. The overexpression of RuvBL1 and RuvBL2 have been reported in different types of cancer, such as gastric cancer, bladder cancer, melanoma, nonsmall cell lung cancer and colon cancer [16] [17] [18]. In vivo silencing study resulted into the blockage of hepatocarcinoma [18] [19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RuvB protein belongs to AAA+ family of enzymes involved in diverse cellular activities. In addition to the annotated two RuvB proteins in Plasmodium falciparum database, we report that a third RuvB protein is also present. The amino acid sequence analysis has revealed that P. falciparum RuvB3 (PfRuvB3) possesses Walker motif A, Walker motif B, sensor I and sensor II conserved motifs similar to yeast and human RuvB like proteins. The phylogenetic analysis revealed that PfRuvB3 is closely related to yeast RuvB like proteins which are essential for the survival of yeast. The biochemical characterization of recombinant PfRuvB3 confirms its ssDNA dependent ATPase activity. Using the truncated derivatives we show that Walker motif A is essential for the enzymatic activity of PfRuvB3. Using the immunodepletion assays we further show that the ATPase activity is attributable to PfRuvB3 protein. The endogenous P. falciparum RuvB3 contains the characteristic ATPase and some DNA helicase activities. The confocal microscopy analysis showed that this protein is mainly expressed during intraerythrocytic schizont stages of the parasite and is localized to the nuclear region. Once merozoite comes out from schizont, PfRuvB3 protein distinctly relocalized to the subnuclear region. The co-localization studies with a nucleolar marker PfNop1 further suggest that in P. falciparum RuvB3 localizes into a discrete nuclear compartment. On the basis of these studies it can be speculated that P. falciparum RuvB3 is most likely required for intraerythrocytic schizogony.
    Full-text · Article · Jun 2012 · Molecular and Biochemical Parasitology
  • Source
    • "Wnt/ˇ-catenin signaling Thirty four core proteins (Table 1) were identified from the Kegg Pathway database ( and the literature (Boonen et al., 2009; DasGupta et al., 2005a; Gehrke et al., 2009; Hirota et al., 2008; Ishitani et al., 1999; Latres et al., 1999; Lauscher et al., 2007; Liu et al., 2001 "
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last few years, researchers have an intense interest in the evolutionarily conserved signaling pathways which have crucial roles during embryonic development. The most intriguing factor of this interest is that malfunctioning of these signaling pathways (Hedgehog, Notch, Wnt etc.) leads to several human diseases, especially to cancer. This study deals with the β-catenin dependent branch of Wnt signaling and the Hedgehog signaling pathways which offer potential targeting points for cancer drug development. The identification of all proteins functioning in these signaling networks is crucial for the efforts of preventing tumor formation. Here, through integration of protein-protein interaction data and Gene Ontology annotations, Wnt/β-catenin and Hedgehog signaling networks consisting of proteins that have statistically high probability of being biologically related to these signaling pathways were reconstructed in Drosophila melanogaster. Next, by the structural network analyses, the crucial components functioning in these pathways were identified. The proteins Arm, Frizzled receptors (Fz and Fz2), Arr, Apc, Axn, Ci and Ptc were detected as the key proteins in these networks. Futhermore, the hub protein Mer having tumor suppressor function may be proposed as a putative drug target for cancer and deserves further investigation via experimental methods. Finally, the crosstalk analysis between the reconstructed networks reveals that these two signaling networks crosstalk to each other.
    Full-text · Article · Oct 2011 · Computational biology and chemistry
Show more