NOLC1, an enhancer of nasopharyngeal carcinoma progression, is essential for TP53 to regulate MDM2 expression
Journal
American Journal of Pathology
Journal Volume
175
Journal Issue
1
Pages
342-354
Date Issued
2009
Author(s)
Abstract
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. Copyright ? American Society for Investigative Pathology.
SDGs
Other Subjects
alpha tubulin; beta actin; gene product; protein MDM2; protein NOLC1; protein p53; short hairpin RNA; unclassified drug; angiogenesis; animal experiment; animal model; apoptosis; article; cancer cell culture; carcinogenesis; cell growth; China; chromatin immunoprecipitation; controlled study; down regulation; enhancer region; gene expression regulation; genetic transfection; human; human cell; MDM2 gene; microarray analysis; mouse; nasopharynx carcinoma; nonhuman; pathogenesis; priority journal; promoter region; proto oncogene; regulatory mechanism; SCID mouse; Singapore; subtractive hybridization; Taiwan; tumor cell; tumor growth
Publisher
American Society for Investigative Pathology Inc.
Type
journal article