Abstract
BackgroundLong interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain.MethodsImmunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases.ResultsMost primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (≥65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation-specific PCR. BLASTP program analysis revealed that GCRG213p peptide shared 83.0% alignment with the C-terminal region of L1 endonuclease (L1-EN). GCRG213p sequence possesses the important residues that compose the conserved features of L1-EN.ConclusionsGCRG213p could be a variant of L1-EN, a functional member of L1-EN family. Overexpression of GCRG213p is common in both primary gastric cancer and lymph node metastasis. These findings provide evidence of somatic L1 expression in gastric cancer, and its potential consequences in the form of tumor.
Highlights
Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed in the germ lines and in somatic tissues
This paper reports our present study that has confirmed the gastric cancer related gene 213 (GCRG213) protein (GCRG213p) expression in gastric cancer cell lines by using monoclonal mouse anti-GCRG213p antibody produced in our laboratory (Geriatric institute, China PLA General Hospital, Beijing, China)
GCRG213p expression patterns in normal gastric mucosa and gastric adenocarcinoma Distinct GCRG213p staining was observed in primary gastric adenocarcinomas, lymph node metastasis tumors, and non-tumoral gastric mucosa (Figure 1)
Summary
Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed in the germ lines and in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Long interspersed nuclear element-1 (LINE-1 or L1) is the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome and comprises about 17% of the human genome [1]. ORF2p is a 150-kDa protein with endonuclease (L1-EN) [6] and reverse transcriptase (L1-RT) [7] activities. The host limits the spread of such elements by transcriptional and post-transcriptional silencing mechanisms that reduce activity to tolerable levels [9]
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