Targets of Wnt/ß-Catenin Transcription in Penile Carcinoma

Arya, Manit; Thrasivoulou, Christopher; Henrique, Rui; Millar, Michael; Hamblin, Ruth; Davda, Reena; Aare, Kristina; Masters, J. R. W.; Thomson, Calum; Muneer, Asıf; Patel, Hitendra; Ahmed, Aamir

doi:10.1371/journal.pone.0124395

Cited by 26 publications

(48 citation statements)

References 45 publications

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“…Other details of the protocol have been described previously [13, 17]. Imaging of the whole tissue array was performed using an Axio Scan Z1 (Carl Zeiss) multifluorophore slide scanner.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

et al. 2016

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Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.

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“…Other details of the protocol have been described previously [13, 17]. Imaging of the whole tissue array was performed using an Axio Scan Z1 (Carl Zeiss) multifluorophore slide scanner.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

et al. 2016

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“…As shown in Figure 1A , the expression of active β-catenin was decreased in hDPC/ Dlx3 cells. CyclinD1, C-myc and Tcf-7 were known as target genes of canonical Wnt/β-catenin signaling pathway ( Arya et al, 2015 ; Kaur et al, 2015 ). As expected, the expressions of CyclinD1, C-myc, and Tcf-7 were also decreased in hDPC/ Dlx3 cells (Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway

Zhan

Gou

et al. 2018

Front. Physiol.

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Homeodomain gene Distal-less-3 (Dlx3) plays an important role during tooth development. Our previous studies indicate that DLX3 inhibits proliferation of human dental pulp cells (hDPCs). However, the mechanism of DLX3 regulating proliferation of hDPCs and maintaining the quiescence of the cells remain unknown. Given the importance of canonical Wnt signaling in the proliferation of dental pulp cell and tooth development, we hypothesized that DLX3 inhibited proliferation of hDPCs through inactivation of canonical Wnt signaling. With overexpression or knock-down of DLX3 in primary hDPCs, we found DLX3 down regulated canonical Wnt signaling and its downstream target genes. And when the DLX3 overexpressed-cells were treated with lithium chloride, the proliferation inhibition by DLX3 was reversed. We also found that DLX3 enhanced the expression of DKK1 and the reduced proliferation of hDPCs by DLX3 was reversed with knock-down of DKK1. Furthermore, luciferase reporter assay and chromatin immunoprecipitation assay showed DLX3 was able to bind to Dkk1 promoter region from nucleotides (nt) -1656 to -1245, and stimulated Dkk1 promoter activity. Mutagenesis studies further revealed two DLX3 responsive elements in Dkk1 promoter. Taken together, our data indicate that DLX3 inhibits proliferation of hDPCs via inactivation of Wnt/β-catenin signaling pathway by directly binding to Dkk1 promoter and increasing its expression.

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“…In addition to analysing expression of ribosomal proteins in prostate tissue, co-localization was also calculated as it might be altered in disease. This approach has been described previously [ 7 , 23 ]. Confocal images of multi-fluorophore, immunofluorescently labelled TA’s were tested for the following antibodies and fluorophores: RPS19 (Cy3 = 559 / 567), RPS21 (FITC, excitation/emission (nm) = 488 / 519), and RPS24 (Cy5 = 635 / 664) using the BondMax system.…”

Section: Methodsmentioning

confidence: 99%

Expression of ribosomal proteins in normal and cancerous human prostate tissue

et al. 2017

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Few quantifiable tissue biomarkers for the diagnosis and prognosis of prostate cancer exist. Using an unbiased, quantitative approach, this study evaluates the potential of three proteins of the 40S ribosomal protein complex as putative biomarkers of malignancy in prostate cancer. Prostate tissue arrays, constructed from 82 patient samples (245 tissue cores, stage pT3a or pT3b), were stained for antibodies against three ribosomal proteins, RPS19, RPS21 and RPS24. Semi-automated Ox-DAB signal quantification using ImageJ software revealed a significant change in expression of RPS19, RPS21 and RPS24 in malignant vs non-malignant tissue (p<0.0001). Receiver operating characteristics curves were calculated to evaluate the potential of each protein as a biomarker of malignancy in prostate cancer. Positive likelihood ratios for RPS19, RPS21 and RPS24 were calculated as 2.99, 4.21, and 2.56 respectively, indicating that the overexpression of the protein is correlated with the presence of disease. Triple-labelled, quantitative, immunofluorescence (with RPS19, RPS21 and RPS24) showed significant changes (p<0.01) in the global intersection coefficient, a measure of how often two fluorophore signals intersect, for RPS19 and RPS24 only. No change was observed in the co-localization of any other permutations of the three proteins. Our results show that RPS19, RPS21 or RPS24 are upregulated in malignant tissue and may serve as putative biomarkers for prostate cancer.

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Targets of Wnt/ß-Catenin Transcription in Penile Carcinoma

Cited by 26 publications

References 45 publications

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway

Expression of ribosomal proteins in normal and cancerous human prostate tissue

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