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Genetic alterations in a telomerase-immortalized human esophageal epithelial cell line: Implications for carcinogenesis
Authors:Pak Yan Cheung  Wen Deng  Cornelia Man  Wan Wai Tse  Gopesh Srivastava  Simon Law  Sai Wah Tsao  Annie L.M. Cheung
Affiliation:1. Cancer Biology Group, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;2. Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;3. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
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.
Keywords:α-SMA, Alpha-smooth muscle actin   EMT, Epithelial-mesenchymal transition   ESCC, Esophageal squamous cell carcinoma   HPV, Human papillomavirus   hTERT, Human telomerase reverse transcriptase   PD, Population doubling
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