This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Genetics of Head & Neck Disease  • Neoplasms of Head & Neck  • Salivary Gland Disorders  • Genetics  • Genetic Counseling/ Testing/ Therapy  • Alert me on articles by topic  Social Bookmarking   What's this?

Lurdes Queimado, MD, PhD; David Obeso, MS; Melissa D. Hatfield, MS; Yonghong Yang, MD, PhD; David M. Thompson, PhD; Antonio M.C. Reis, MD

Arch Otolaryngol Head Neck Surg. 2008;134(1):94-101.

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

Design  The expression of WIF1, WNT1, and β-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.

Subjects  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. β-Catenin messenger RNA expression was significantly up-regulated in salivary gland tumor cells. A positive linear correlation between β-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 β-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.

Author Affiliations: Departments of Otorhinolaryngology (Drs Queimado and Yang, Mr Obeso, and Ms Hatfield), Biostatistics and Epidemiology (Dr Thompson), and Dermatology (Dr Reis), University of Oklahoma Health Sciences Center, Oklahoma City.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?