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

Pak Yan Cheung; Wen Deng; Cornelia Man; Wan Wai Tse; Gopesh Srivastava; Simon Law; Sai Wah Tsao; Annie L M Cheung

doi:10.1016/j.canlet.2009.12.015

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

Cancer Lett. 2010 Jul 1;293(1):41-51. doi: 10.1016/j.canlet.2009.12.015. Epub 2010 Jan 21.

Authors

Pak Yan Cheung¹, 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.

PMID: 20092939
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 p16(INK4a) 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 p16(INK4a) on cyclin D1. These findings probably represent early crucial events and mechanisms in esophageal carcinogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / genetics
Cell Growth Processes / genetics
Cell Line, Transformed
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology*
Cellular Senescence / genetics
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 Neoplasms / genetics*
Esophageal Neoplasms / metabolism
Esophageal Neoplasms / pathology
Esophagus / metabolism
Esophagus / pathology
Esophagus / physiology*
Humans
Male
Mice
Mice, Nude
Middle Aged
Neoplasms, Squamous Cell / genetics*
Neoplasms, Squamous Cell / metabolism
Neoplasms, Squamous Cell / pathology
Retinoblastoma Protein / biosynthesis
Retinoblastoma Protein / genetics
Retinoblastoma Protein / metabolism
Spectral Karyotyping
Telomerase / biosynthesis
Telomerase / genetics*
Transfection

Substances

Cyclin-Dependent Kinase Inhibitor p16
E2F1 Transcription Factor
E2F1 protein, human
Retinoblastoma Protein
TERT protein, human
Telomerase