Decreased expression of catenins (? and ?), p120 CTN, and E-cadherin cell adhesion proteins and E-cadherin gene promoter methylation in prostatic adenocarcinomas

Kallakury, Bhaskar; Sheehan, E B S Christine; Winn-Deen, Emily S.; Oliver, B.; Fisher, Hugh A.G.; Kaufman, Ronald P.; Ross, Jeffrey S.

doi:10.1002/1097-0142(20011201)92:11<2786::aid-cncr10128>3.0.co;2-i

Cited by 106 publications

(54 citation statements)

References 57 publications

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“…These include decrease or lack of E-cadherin/catenin expression by mutations and deletions in the genes encoding E-cadherin or catenin, promoter hypermethylation of E-cadherin, or post-translational modifications. 4,6,45,[49][50][51] To look into the specific possible causes of the downregulation of E-cadherin, we studied the DNA methylation status of its promoter region in tumors with reduced expression, since aberrant hypermethylation was demonstrated to be one of the most important mechanisms of inactivation of this adhesion protein in human 7 and mouse 52 cancer. Our results revealed that the promoter hypermethylation of E-cadherin may be an important mechanism for its repression in our rat model.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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Loss of the epithelial phenotype and disruption of adhesion molecules is a hallmark in the epithelialmesenchymal transition (EMT) reported in several types of cancer. Most of the studies about the relevance of adhesion and junction molecules in lung cancer have been performed using established tumors or in vitro models. The sequential molecular events leading to EMT during lung cancer progression are still not well understood. We have used a rat model for multistep lung carcinogenesis to study the status of adherens and tight junction proteins and mesenchymal markers during EMT. After silica-induced chronic inflammation, rats sequentially develop epithelial hyperplasia, preneoplastic lesions, and tumors such as adenocarcinomas and squamous cell carcinomas. In comparison with normal and hyperplastic bronchiolar epithelium and with hyperplastic alveolar type II cells, the expression levels of E-cadherin, a-catenin and b-catenin were significantly reduced in adenomatoid preneoplastic lesions and in late tumors. The loss of E-cadherin in tumors was associated with its promoter hypermethylation. a-and b-catenin dysregulation lead to cytoplasmic accumulation in some carcinomas. No nuclear b-catenin localization was found at any stage of any preneoplastic or neoplastic lesion. Zonula occludens protein-1 was markedly decreased in 66% of adenocarcinomas and in 100% squamous cell carcinomas. The mesenchymal-associated proteins N-cadherin and vimentin were analyzed as markers for EMT. N-cadherin was de novo expressed in 32% of adenocarcinomas and 33% of squamous cell carcinomas. Vimentin-positive tumor cells were found in 35% of adenocarcinomas and 88% of squamous cell carcinomas. Mesenchymal markers were absent in precursor lesions, both hyperplastic and adenomatoid. The present results show that silica-induced rat lung carcinogenesis is a good model to study EMT in vivo, and also provide in vivo evidence suggesting that the changes in cell-cell adhesion molecules are an early event in lung carcinogenesis, while EMT occurs at a later stage.

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Section: Discussionmentioning

confidence: 99%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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“…Using a semiquantitative scale that was described previously, 20 an exclusively membranous pattern of staining was considered positive for E-cadherin expression. Both the intensity of staining and the distribution as an approximate percentage of positive tumor cells were considered in the assessment.…”

Section: Assessment Of Immunoreactivitymentioning

confidence: 99%

DNA methyltransferase 1 expression and promoter methylation of E‐cadherin in mucoepidermoid carcinoma

Shieh

Shiah

Jeng

et al. 2005

Cancer

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Cervical neoplasia is attributed to a persistent Human Papilloma Virus infection. The Pap smear being the mainstay of cervical cancer screening in low‐resource settings, we studied the nonclassical features which might indicate HPV infection. These included abortive koilocytes, mild dyskeratosis, parakeratosis, mild nuclear hyperchromasia, bi/multinucleation, measles cells, and keratohyaline‐like granules. Two hundred and eight women with a satisfactory Pap smear and a Hybrid Capture II test were compared against the “HPV Gold Standard” for validation of the nonclassical signs. This was defined as one with any/all of the following: definite HPV‐related lesions on Pap smear (LSIL and above), hrHPV positivity, and CIN I, or above on histology. The highest PPV and NPV were achieved by bi/multinucleation and mild nuclear hyperchromasia, respectively. The mean number of nonclassical signs for HPV Gold Standard‐positive and ‐negative groups was 5.52 and 3.12 per smear, respectively (P < 0.0005). Abortive koilocytes, mild dyskeratosis, mild nuclear hyperchromasia, bi/multinucleation, parakeratosis, and diffuse keratohyaline granules had the best correlation with the gold standard (P < 0.05). Addition of nonclassical signs to established intraepithelial lesions on Pap smear increased the sensitivity from 52.31to 59.10% and reduced the specificity from 100 to 98%. To maximize the benefit from grouping of these signs, various combinations were studied. The best was: abortive koilocytes, mild nuclear hyperchromasia, and bi/multinucleation. Another was abortive koilocytes, mild nuclear hyperchromasia, bi/multinucleation, and mild dyskeratosis. In conclusion, these signs proved useful for identifying HPV infection. Population‐based studies are required to corroborate our findings. Diagn. Cytopathol. 2010;38:645–651. © 2009 Wiley‐Liss, Inc.

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“…Ninety-five percent of the PC values fell below a threshold that excluded all benign prostatic hyperplasia and prostatitis specimens combined; suggesting that altered expression of proteins in the cadherin/catenin complex may identify PC field disease/effect. A study by Kallakury et al (21) supports this conclusion. The investigators applied immunohistochemistry to an analysis of selected proteins of the catenin/cadherin complex in PC, comparing expression in the cancerous epithelium to expression in the noncancerous epithelium of cancer-bearing prostate glands.…”

Section: Discussionmentioning

confidence: 81%

“…h-Catenin is a 92-kDa protein encoded by a gene localized to human chromosome 3p22 (21). The protein expresses both cell adhesion and transcriptional regulation functions that are independent of each other.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Fluorescence Imaging Analysis for Cancer Biomarker Discovery: Application to β-Catenin in Archived Prostate Specimens

Huang¹,

Casale²,

Tian

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The surprising disparity between the number of proteinencoding genes (f30,000) in the human genome and the number of proteins (f300,000) in the human proteome has inspired the development of translational proteomics aimed at protein expression profiling of disease states. Translational proteomics, which offers the promise of early disease detection and individualized therapy, requires new methods for the analysis of clinical specimens. We have developed quantitative flourescence imaging analysis (QFIA) for accurate, reproducible quantification of proteins in slidemounted tissues. The method has been validated for the analysis of B-catenin in archived prostate specimens fixed in formalin. QFIA takes advantage of the linearity of fluorescence antibody signaling for tissue epitope content, a feature validated for B-catenin in methacarn-fixed prostate specimens analyzed by reverse-phase protein array analysis and QFIA (r = 0.97). QFIA of B-catenin in formaldehyde-fixed tissues correlated directly with B-catenin content (r = 0.86). Application of QFIA in a cross-sectional study of biopsies from 42 prostate cancer (PC) cases and 42 matched controls identified B-catenin as a potential field marker for PC. Receiver operating characteristic plots revealed that Bcatenin expression in the normal-appearing acini of cancerous glands identified 42% (95% confidence intervals, 26-57%) of cancer cases, with 88% (95% confidence intervals, 80-96%) specificity. The marker may contribute to a PC biomarker panel. In conclusion, we report the development and validation of a new method for fluorescence quantification of proteins in archived tissues and its application to archived specimens for an evaluation of B-catenin expression as a biomarker for PC. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1371 -81)

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Decreased expression of catenins (? and ?), p120 CTN, and E-cadherin cell adhesion proteins and E-cadherin gene promoter methylation in prostatic adenocarcinomas

Cited by 106 publications

References 57 publications

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

DNA methyltransferase 1 expression and promoter methylation of E‐cadherin in mucoepidermoid carcinoma

Quantitative Fluorescence Imaging Analysis for Cancer Biomarker Discovery: Application to β-Catenin in Archived Prostate Specimens

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