Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma
Open Access
- 26 March 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 26 (40), 5877-5888
- https://doi.org/10.1038/sj.onc.1210390
Abstract
By comparative DNA fingerprinting, we identified a 357-bp DNA fragment frequently amplified in esophageal squamous cell carcinomas (ESCC). This fragment overlaps with an expressed sequence tag mapped to 7q22. Further 5′ and 3′-rapid amplification of cDNA ends revealed that it is part of a novel, single-exon gene with full-length mRNA of 2052 bp and encodes a nuclear protein of 109 amino acids (∼15 kDa). This gene, designated as gene amplified in esophageal cancer 1 (GAEC1), was located within a 1–2 Mb amplicon at 7q22.1 identified by high-resolution 1 Mb array- comparative genomic hybridization in 6/10 ESCC cell lines. GAEC1 was ubiquitously expressed in normal tissues including esophageal and gastrointestinal organs; with amplification and overexpression in 6/10 (60%) ESCC cell lines and 34/99 (34%) primary tumors. Overexpression of GAEC1 in 3T3 mouse fibroblasts caused foci formation and colony formation in soft agar, comparable to H-ras and injection of GAEC1-transfected 3T3 cells into athymic nude mice formed undifferentiated sarcoma in vivo, indicating that GAEC1 is a transforming oncogene. Although no significant correlation was observed between GAEC1 amplification and clinicopathological parameters and prognosis, our study demonstrated that overexpressed GAEC1 has tumorigenic potential and suggest that overexpressed GAEC1 may play an important role in ESCC pathogenesis.This publication has 23 references indexed in Scilit:
- Overexpression of theRADICAL-INDUCED CELL DEATH1(RCD1) Gene of Arabidopsis Causes Weakrcd1Phenotype with Compromised Oxidative-Stress ResponsesBioscience, Biotechnology, and Biochemistry, 2006
- Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylationOncogene, 2005
- Distinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells: whole-genome evidence from multiple cell linesOncogene, 2004
- High-resolution analysis of genomic copy number alterations in bladder cancer by microarray-based comparative genomic hybridizationOncogene, 2004
- Molecular Cytogenetic Analysis of 17 Renal Cancer Cell Lines: Increased Copy Number at 5q31-33 in Cell Lines from Nonpapillary CarcinomasJapanese Journal of Cancer Research, 2000
- Comparative Genomic Hybridization Studies in Hydatidiform Moles and ChoriocarcinomaCancer Genetics and Cytogenetics, 2000
- Chromosomal imbalances in adult T-cell leukemia revealed by comparative genomic hybridization: gains at 14q32 and 2p16-22 in cell linesJournal of Human Genetics, 1999
- Casein kinase II in signal transduction and cell cycle regulationMolecular and Cellular Biochemistry, 1993
- PCR Amplification from Paraffin-Embedded Tissues: Effects of Fixative and Fixation TimeAmerican Journal of Clinical Pathology, 1991
- An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAsNucleic Acids Research, 1987