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Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas

Audard, Virginie
Cavard, Catherine
Richa, Hubert
Couvelard, Anne
Sauvanet, Alain
Terris, Benoit
Paye, Francois
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Published in Pancreas. 2008, vol. 36, no. 1, p. 80-83
Abstract OBJECTIVES: To analyze in solid pseudopapillary neoplasm of the pancreas (SPNP) the consequences of the deregulated Wnt pathway by studying the expression of Wnt target glutamine synthetase (GLUL), cyclin D1, and E-cadherin, which is one of the beta-catenin binding partner in cell adhesion. METHODS: The expression of cyclin D1 and GLUL was studied at the protein and/or messenger RNA levels, and the immunolocalization for E-cadherin was analyzed in 28 SPNPs screened for beta-catenin mutations. Expression of cyclin D1, GLUL, and beta-catenin was also assessed in pancreatic endocrine tumors as controls. RESULTS: Cytosolic and/or nuclear accumulation of beta-catenin was observed in all tumors; an activating beta-catenin mutation was identified in 21 (91%) of 23 tumors analyzed. E-cadherin expression is lost from the membrane and is observed in intracytosolic "dotlike" structures. Whereas cyclin D1 expression is observed widely in SPNP and endocrine tumors, GLUL expression is restricted to SPNP (100%) and rare endocrine tumors (10%) displaying Wnt activation. CONCLUSIONS: The activation of the Wnt/beta-catenin pathway in SPNP has 2 main consequences. First, E-cadherin expression moved from membranous to intracytoplasmic localization. Second, GLUL expression is highly correlated with Wnt/beta-catenin activation, demonstrating its faithfulness as a Wnt target gene.
Keywords AdultCadherins/analysis/*geneticsCarcinoma, Pancreatic Ductal/chemistry/geneticsCell Membrane/chemistryCyclin D1/geneticsCytoplasm/chemistryDNA Mutational AnalysisFemale*Gene ExpressionGlutamate-Ammonia Ligase/*geneticsHumansImmunohistochemistryMalePancreatic Neoplasms/chemistry/*geneticsReverse Transcriptase Polymerase Chain ReactionSignal TransductionWnt Proteins/physiologyBeta Catenin/analysis/physiology
PMID: 18192886
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AUDARD, Virginie et al. Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas. In: Pancreas, 2008, vol. 36, n° 1, p. 80-83. doi: 10.1097/mpa.0b013e318137a9da https://archive-ouverte.unige.ch/unige:19620

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Deposited on : 2012-04-23

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