Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types

Background: There are now several lines of evidence to suggest that protein synthesis and translation factors are involved in the regulation of cell proliferation and cancer development. Aims: To investigate gene expression patterns of eukaryotic releasing factor 3 (eRF3) in gastric cancer. Methods: RNA was prepared from 25 gastric tumour biopsies and adjacent non-neoplastic mucosa. Real time TaqMan reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the relative gene expression levels. DNA was isolated from tumour and normal tissues and gene dosage was determined by a quantitative real time PCR using SYBR Green dye. Results: Different histological types of gastric tumours were analysed and nine of the 25 tumours revealed eRF3/GSPT1 overexpression; moreover, eight of the 12 intestinal type carcinomas analysed overexpressed the gene, whereas eRF3/GSPT1 was overexpressed in only one of the 10 diffuse type carcinomas (Kruskal-Wallis Test; p , 0.05). No correlation was found between ploidy and transcript expression levels of eRF3/GSPT1. Overexpression of eRF3/GSPT1 was not associated with increased translation rates because the upregulation of eRF3/GSPT1 did not correlate with increased eRF1 levels. Conclusions: Overexpression of eRF3/GSPT1 in intestinal type gastric tumours may lead to an increase in the translation efficiency of specific oncogenic transcripts. Alternatively, eRF3/GSPT1 may be involved in tumorigenesis as a result of its non-translational roles, namely (dis)regulating the cell cycle, apoptosis, or transcription.

Unesp Ciência, 2009, ano 1, número 3

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2011, ano 3, número 23

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2011, ano 3, número 24

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2011, ano 3, número 25

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2011, ano 3, número 26

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 27

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 28

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 29

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 30

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 31

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 32

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 33

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2012, ano 3, número 34

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donors

Thymidylate synthase, as a rate-limiting step in DNA synthesis, catalyses the conversion of dUMP into dTMP using 5,10-methylenotetrahydrofolate as the methyl donor. Two polymorphisms have been described in this gene: a repeat polymorphism in the 5' promoter enhancer region (3R versus 2R) and a 6 bp deletion in the 3' unstranslated region. Both of these may affect protein levels. The present case control study was aimed at investigating the influence of these two polymorphisms on the development of colorectal cancer (CRC), as well as their potential interaction with folate, vitamin B6 and vitamin B12 intake. A total of 196 cases and 200 controls, matched for age and sex distribution, were included in the study. No association was found between CRC and the 28 bp repeat polymorphism, but it was observed that individuals with the 6 bp/del and del/del genotypes had a significantly lower risk of developing the disease (OR=0.47; 95% CI 0.30-0.72). A combined genotype (2R/2R; 6 bp/del+del/del) was also found, which was associated with an even lower risk of developing of the disease (OR=0.42; 95% CI 0.26-0.69). No significant interaction between these polymorphisms and vitamin intake was observed. These results indicate for the first time that the 6 bp/del allele might be a protective factor in the development of CRC, independent of the intake of methyl group donors.