Original contributionOverexpression of EIF-5A2 is associated with metastasis of human colorectal carcinoma☆
Introduction
Colorectal carcinoma (CRC) is the fourth most common human malignancy and a major cause of cancer-related death in developed countries [1]. The incidence of CRC in China increased rapidly during the past 2 decades [2]. The pathogenesis of CRC is believed to be a multistep process that involves multiple genetic changes, including inactivation of tumor suppressor genes and activation of oncogenes. Although CRC has been widely studied, the precise genetic changes underlying the development and progression of this neoplasm are not thoroughly understood. Amplification of 3q is one the most frequent chromosomal aberrations in CRC detected by comparative genomic hybridization [3], [4]. Amplification of 3q also has been detected frequently in many other human cancers including ovarian [5], lung [6], esophagus [7], gastric [8] carcinomas, and others [9], [10], [11]. These studies strongly suggest that the existence of oncogene(s) at 3q plays an important role in the pathogenesis and progression of a number of different human solid tumors.
Using a chromosome microdissection-hybrid selection method, we have previously isolated a novel candidate oncogene, eIF-5A2 (eukaryotic initiation factor 5A2), from a primary ovarian cancer containing high–copy-number amplification of 3q26 [12]. EIF-5A2 protein shares 82% identical amino acid sequence with EIF-5A including the minimum domain needed for EIF-5A maturation by hypusine modification at lysine-50 residue. Previous study showed that intracellular depletion of eIF-5A could cause the inhibition of cell growth [13]. Other studies indicated that the inhibition of deoxyhypusine synthase (DHPS), the enzyme involved in the hypusination reaction of eIF-5A, could inhibit Chinese hamster ovary cells proliferation [14], suppress the growth of HeLa cells, and induce apoptosis [15]. Recently, the tumorigenic characteristics of eIF-5A2 have also been demonstrated by both in vitro and in vivo assays [12], [16], [17]. In addition, overexpression of EIF-5A2 has been observed to correlate with late clinical stage in ovarian cancer [17]. Because amplification of 3q was also frequently detected in CRC, we hypothesized that eIF-5A2 may also play an important role in the development and progression of CRC. In the present study, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to examine the distribution and frequency of protein expression and amplification of eIF-5A2 in a large group of human CRCs by tissue microarray (TMA).
Section snippets
Patients and tissue specimens
In this study, 139 patients with CRC who underwent partial coloproctectomy were selected consecutively from the surgical pathology archives of the Department of Pathology, Cancer Center and the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, between 1995 and 2003. Patients with mucinous carcinoma and/or familial CRC were excluded from this study. All CRCs selected were conventional adenocarcinoma, in which the 22 cases encountered were colorectal adenomatous polyps in the
EIF-5A2 expression in colorectal tissues
In the present study, the protein expression of EIF-5A2 was investigated by IHC in colorectal tissue TMAs, which contained 139 cases of adjacent normal colorectal mucosa and different colorectal lesions including 139 cases of primary CRC, 22 premalignant colorectal adenomas, and 42 metastases from the same patients with CRC. EIF-5A2 expression could be evaluated informatively in 102 (73.4%) of 139 normal colorectal mucosa, 17 (77.3%) of 22 colorectal adenomas, 126 (90.6%) of 139 primary CRCs,
Discussion
Our previous studies provide evidence that the eIF-5A2 gene, located at human chromosome 3q26, has an oncogenic function in ovarian carcinoma [12], [17]. Because amplification of 3q was frequently detected in human CRCs [3], [4], it is highly possible that the abnormalities of eIF-5A2 may play a critical role in colorectal tumorigenesis.
In the present study, the expression of EIF-5A2 was first investigated by IHC using TMA containing a series of normal colorectal and tumor tissues (benign and
References (24)
- et al.
Recurrent genetic alterations in 26 colorectal carcinomas and 21 adenomas from Chinese patients
Cancer Genet Cytogenet
(2003) - et al.
Recurrent chromosome alterations in primary ovarian carcinoma in Chinese women
Cancer Genet Cytogenet
(2002) - et al.
A broad amplification pattern at 3q in squamous cell lung cancer—a fluorescence in situ hybridization study
Cancer Genet Cytogenet
(2000) - et al.
Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization
Cancer Genet Cytogenet
(2000) - et al.
Is hypusine essential for eukaryotic cell proliferation?
Trends Biochem Sci
(1993) - et al.
Antiproliferative effects of inhibitors of deoxyhypusine synthase. Inhibition of growth of Chinese hamster ovary cells by guanyl diamines
J Biol Chem
(1994) - et al.
Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma
Hum Pathol
(2005) - et al.
Recent progress in understanding mechanisms of mammalian DNA amplification
Cell
(1989) Colorectal cancer: molecules and populations
J Natl Cancer Inst
(1999)- et al.
Cancer incidence trends in urban Shanghai, 1972-1994: an update
Int J Cancer
(1999)
Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors
Genes Chromosomes Cancer
Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations
Genes Chromosomes Cancer
Cited by (65)
EIF5A2 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells
2022, Clinics and Research in Hepatology and GastroenterologyTranslating Hedgehog in Cancer: Controlling Protein Synthesis
2016, Trends in Molecular MedicineThe translation factor eIF5A and human cancer
2015, Biochimica et Biophysica Acta - Gene Regulatory MechanismsCitation Excerpt :As with eIF5A1, the regulation of eIF5A2 expression is poorly understood although advances are being made. The EIF5A2 gene is often, but not invariably, amplified in cancers and cancer cell lines [12,35,59,74,75,80]. While tumors exhibiting gene amplification generally exhibit high eIF5A2 expression, many have high eIF5A2 levels without gene amplification so additional mechanisms of up-regulation must exist.
MicroRNA-577/EIF5A2 axis suppressed the proliferation of DDP-resistant nasopharyngeal carcinoma cells by blocking TGF-β signaling pathway
2023, Chemical Biology and Drug DesignRisk evaluation and prevention of China's investment in countries along the belt and road
2023, Journal of Intelligent and Fuzzy Systems
- ☆
This study was supported by grants from 985-II Project of State Key Laboratory of Oncology in Southern China, the Foundation of Guangzhou Science and Technology Bureau (2005J1-C0311), the National Nature Science Foundation of China (30300401), and the Sun Yat-sen University “Hundred Talents Program” (85000-3171311).