Published online before print June 18, 2009

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: ajpath.2009.080931v1 175/1/342    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hwang, Y.-C. Articles by Lin, C.-T. Search for Related Content PubMed PubMed Citation Articles by Hwang, Y.-C. Articles by Lin, C.-T.

(American Journal of Pathology. 2009;175:342-354.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080931

NOLC1, an Enhancer of Nasopharyngeal Carcinoma Progression, Is Essential for TP53 to Regulate MDM2 Expression

Yu-Chyi Hwang^*, Tung-Ying Lu^*, Dah-Yeou Huang^*, Yuan-Sung Kuo, Cheng-Fu Kao, Ning-Hsing Yeh, Han-Chung Wu^* and Chin-Tarng Lin^*

From the Institute of Pathology,^* College of Medicine, National Taiwan University, Taipei; the Department of Pathology, National Taiwan University Hospital, National Taiwan University, Taipei; the Institute of Cellular and Organismic Biology, Academic Sinica, Taipei; and the Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei, Taiwan

Nasopharyngeal carcinoma (NPC) is one of the most common cancers among Chinese living in South China, Singapore, and Taiwan. At present, its etiological factors are not well defined. To identify which genetic alterations might be involved in NPC pathogenesis, we identified genes that were differentially expressed in NPC cell lines and normal nasomucosal cells using subtractive hybridization and microarray analysis. Most NPC cell lines and biopsy specimens were found to have higher expression levels of the gene encoding nucleolar and coiled-body phosphoprotein 1 (NOLC1) as compared with normal cells. Severe combined immunodeficiency mice bearing NPC xenografts derived from NOLC1-short hairpin-RNA-transfected animals were found to have 82% lower levels of tumor growth than control mice as well as marked tumor cell apoptosis. Measuring the expression levels of genes related to cell growth, apoptosis, and angiogenesis, we found that the MDM2 gene was down-regulated in the transfectants. Both co-transfection and chromatin immunoprecipitation experiments showed that tumor protein 53-regulated expression of the MDM2 gene requires co-activation of NOLC1. These findings suggest that NOLC1 plays a role in the regulation of tumorigenesis of NPC and demonstrate that both NOLC1 and tumor protein 53 work together synergistically to activate the MDM2 promoter in NPC cells.