Genetic alterations in a telomerase-immortalized human esophageal epithelial cell line: Implications for carcinogenesis

• Published in: Cancer letters 2010-07, Vol.293 (1), p.41-51
• Main Authors: Cheung, Pak Yan, Deng, Wen, Man, Cornelia, Tse, Wan Wai, Srivastava, Gopesh, Law, Simon, Tsao, Sai Wah, Cheung, Annie L.M
• Format: Article
• Language: English
• Subjects: Acquisitions & mergers; Animals; Cancer; Cell culture; Cell cycle; Cell Differentiation - genetics; Cell division; Cell Growth Processes - genetics; Cell Line, Transformed; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cellular Senescence - genetics; Chromosomes; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA Methylation; E2F1 Transcription Factor - biosynthesis; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Epithelial Cells - pathology; Esophageal; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophagus - metabolism; Esophagus - pathology; Esophagus - physiology; Hematology, Oncology and Palliative Medicine; Human papillomavirus; Humans; Immortalization; Karyotype; Male; Mice; Mice, Nude; Middle Aged; Mortality; Neoplasms, Squamous Cell - genetics; Neoplasms, Squamous Cell - metabolism; Neoplasms, Squamous Cell - pathology; p16 INK4a; Potassium; Retinoblastoma Protein - biosynthesis; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; Spectral Karyotyping; Telomerase; Telomerase - biosynthesis; Telomerase - genetics; Transfection
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2009.12.015

Abstract Ectopic expression of viral oncoproteins disrupts cellular functions and limits the value of many existing immortalization models as models for carcinogenesis, especially for cancers without definitive viral etiology. Our newly established telomerase-immortalized human esophageal epithelial cell line, NE2-hTERT, retained nearly-diploid and non-tumorigenic characteristics, but exhibited genetic and genomic alterations commonly found in esophageal cancer, including progressive loss of the p16INK4a alleles, upregulation of anti-apoptotic proteins, epithelial-mesenchymal transition, whole-chromosome 7 gain and duplicated 5q arm. Our data also revealed a novel positive regulation of p16INK4a on cyclin D1. These findings probably represent early crucial events and mechanisms in esophageal carcinogenesis.