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

被引：26

作者：

Cheung, Pak Yan ^{[1
]}

Deng, Wen ^{[1
]}

Man, Cornelia ^{[1
]}

Tse, Wan Wai ^{[1
]}

Srivastava, Gopesh ^{[2
]}

Law, Simon ^{[3
]}

Tsao, Sai Wah ^{[1
]}

Cheung, Annie L. M. ^{[1
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Canc Biol Grp, Pokfulam, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Pokfulam, Hong Kong, Peoples R China

[3] Univ Hong Kong, Li Ka Shing Fac Med, Dept Surg, Pokfulam, Hong Kong, Peoples R China

来源：

CANCER LETTERS | 2010年 / 293卷 / 01期

关键词：

Esophageal; Telomerase; Immortalization; p16(INK4a); Karyotype; BARRETTS-ESOPHAGUS; REVERSE-TRANSCRIPTASE; PROMOTER REGION; T-ANTIGEN; KERATINOCYTES; ABERRATIONS; P16(INK4A); EXPRESSION; DYSPLASIA; GROWTH;

D O I：

10.1016/j.canlet.2009.12.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：41 / 51

页数：11

共 48 条

[1]

Bailey T, 1998, AM J PATHOL, V152, P135

[2] Extension of life-span by introduction of telomerase into normal human cells [J].

Bodnar, AG ;

Ouellette, M ;

Frolkis, M ;

Holt, SE ;

Chiu, CP ;

Morin, GB ;

Harley, CB ;

Shay, JW ;

Lichtsteiner, S ;

Wright, WE .

SCIENCE, 1998, 279 (5349) :349-352

[3] Molecular cytogenetic characterization of tenosynovial giant cell tumors [J].

Brandal, P ;

Bjerkehagen, B ;

Heim, S .

NEOPLASIA, 2004, 6 (05) :578-583

[4] Human telomerase and its regulation [J].

Cong, YS ;

Wright, WE ;

Shay, JW .

MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2002, 66 (03) :407-+

[5] Methylation of the p16INK4a promoter region in telomerase immortalized human keratinocytes co-culturedwith feeder cells [J].

Darbro, B. W. ;

Lee, K. M. ;

Nguyen, N. K. ;

Domann, F. E. ;

Klingelhutz, A. J. .

ONCOGENE, 2006, 25 (56) :7421-7433

[6] Distinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells: whole-genome evidence from multiple cell lines [J].

Deng, W ;

Tsao, SW ;

Guan, XY ;

Lucas, JN ;

Si, HX ;

Leung, CS ;

Mak, P ;

Wang, LD ;

Cheung, ALM .

ONCOGENE, 2004, 23 (56) :9090-9101

[7] Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer [J].

Gockel, Ines ;

Moehler, Markus ;

Frerichs, Kirsten ;

Drescher, Daniel ;

Trinh, Tran Tong ;

Duenschede, Friedrich ;

Borschitz, Thomas ;

Schimanski, Katrin ;

Biesterfeld, Stefan ;

Herzer, Kerstin ;

Galle, Peter R. ;

Lang, Hauke ;

Junginger, Theodor ;

Schimanski, Carl C. .

ONCOLOGY REPORTS, 2008, 20 (04) :845-850

[8] Creating oral squamous cancer cells: A cellular model of oral-esophageal carcinogenesis [J].

Goessel, G ;

Quante, M ;

Hahn, WC ;

Harada, H ;

Heeg, S ;

Suliman, Y ;

Doebele, M ;

von Werder, A ;

Fulda, C ;

Nakagawa, H ;

Rustgi, AK ;

Blum, HE ;

Opitz, OG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15599-15604

[9]

Harada H, 2003, MOL CANCER RES, V1, P729

[10] LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS [J].

HAYFLICK, L .

EXPERIMENTAL CELL RESEARCH, 1965, 37 (03) :614-&

← 1 2 3 4 5 →