Dysregulation of Wnt pathway components in human salivary gland tumors.
OBJECTIVE
To determine the expression level of the Wnt components-WIF1 (Wnt inhibitory factor 1), WNT1, and beta-catenin-in salivary gland tumor cells and to investigate the mechanisms that contribute to activation of the Wnt pathway in human salivary gland tumors.


METHODS
The expression of WIF1, WNT1, and beta-catenin in salivary gland normal tissue and tumor cell lines was analyzed by reverse transcription-polymerase chain reaction and Western blot analysis. A relationship between the expression of distinct genes was determined by Pearson correlation. The presence of rearrangements involving WIF1 was evaluated by reverse transcription-polymerase chain reaction analysis.


METHODS
Samples were obtained from 6 normal salivary glands and 10 cell lines established from primary benign and malignant salivary gland tumors.


RESULTS
The expression of WIF1 was high in normal salivary gland tissue but was significantly down-regulated in all salivary gland tumor cell lines analyzed (P < .001). The WIF1 rearrangements were recurrent but rare in salivary gland tumors. Expression of WNT1 protein was undetectable in normal tissue but readily detectable by Western blot analysis in all salivary gland tumor cell lines. beta-Catenin messenger RNA expression was significantly up-regulated in salivary gland tumor cells. A positive linear correlation between beta-catenin and PLAG1 (pleomorphic adenoma gene 1) gene expression was observed.


CONCLUSIONS
This is the first report (to our knowledge) showing down-regulation of an antagonist of the Wnt pathway, WIF1, and up-regulation of a Wnt agonist, WNT1, in salivary gland tumor cells. This dysregulation of WNT1 and WIF1 expression, coupled with the observed increase in beta-catenin transcription, may consequently promote salivary gland oncogenesis. Our data support the study of the Wnt pathway as a putative therapeutic target for salivary gland cancer.
Queimado
Lurdes
L
Department of Otorhinolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. lurdes-queimado@ouhsc.edu
Obeso
David
D
Hatfield
Melissa D
MD
Yang
Yonghong
Y
Thompson
David M
DM
Reis
Antonio M C
AM
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C104382:PLAG1 protein, human; D012097:Repressor Proteins; C485569:WIF1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin