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Oncol Rep. 2008 Jun;19(6):1421-7.

Loss of CYLD might be associated with development of salivary gland tumors.

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  • 1Second Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan.


Molecular studies of cylindromas, which arise from the eccrine or apocrine cells of the skin, have demonstrated frequent alterations at chromosome 16q12-13, recently found to house the cylindromatosis (CYLD) gene. CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Loss of the deubiquitinating activity of CYLD is correlated with tumorigenesis. It has been reported that the expression of CYLD is observed in various organs. We demonstrated previously that human salivary gland tumor (SGT) cell line, HSG spontaneously expresses CYLD and also found that adenoid cystic carcinoma (ACC) arising from the hard palate was distinctly positive for CYLD, immunohistochemically. However, it is unclear whether loss of CYLD is associated with development of SGTs. This study examined CYLD function in SGT cells and attempted to clarify whether CYLD is associated with development of SGTs. The expression of CYLD and NF-kappaB mRNAs in HSG cells was increased by TNF-alpha. Translocation of NF-kappaB protein from the cytoplasm to the nucleus in HSG cells peaked at 30 min after TNF-alpha stimulation, then decreased at 60 min, whereas that of CYLD protein increased gradually in a time-dependent manner. Luciferase reporter assay indicated that TNF-alpha induced a 5-fold increase of NF-kappaB-dependent transcription at 4 h, which was further enhanced by knockdown of CYLD using RNA interference. Taken together, these data demonstrated that the levels of both CYLD and NF-kappaB mRNAs accumulated in HSG cells during 24 h after TNF-alpha stimulation, although the NF-kappaB activity in the cells was at least negatively regulated by CYLD. Immunohistochemical examinations revealed that there are several correlations between the expression of CYLD and NF-kappaB-related factors in 17 cases of ACC tissues. These findings suggest that loss of CYLD is associated with development of SGTs.

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