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AGER

advanced glycosylation end product-specific receptor;AGER;advanced glycosylation end product-specific receptor

RAGE isoform NtRAGE-delta|RAGE isoform sRAGE-delta|receptor for advanced glycation end-products variant 20

6p21.3

protein-coding

The clinical relevance of the receptor for advanced glycation end products (RAGE) and amphoterin expression was examined in 119 non-diabetic patients with colorectal carcinoma. expression of RAGE was examined by immunohistochemistry and that of amphoterin by in situ hybridization. RAGE expression was observed in 55% (64/119) of the cases. RAGE positivity in Dukes B, C and D cases was 19, 81 and 100%, respectively (p<0.0001). Amphoterin was expressed in most cases regardless of tumor stage. Survival analysis of Dukes B and C cases showed a significantly poorer prognosis for patients with co-expression of RAGE and amphoterin than for patients without co-expression. The results suggest that co-expression of RAGE and amphoterin is closely associated with invasion and metastasis of colorectal cancer.

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, contributes to multiple pathologies including cancer. Early growth response 1 (EGR1) is a tumor suppressor gene or a tumor promoter involved in tumorigenesis and progression of some cancers. However, there is some lack of knowledge about the expression and clinical significance of RAGE and EGR1 in human primary gastric adenocarcinoma (GAC). The present study was aimed to investigate the expression and clinical significance of RAGE and EGR1 in human GAC. One hundred and twenty cases of GAC tissues, adjacent non-cancer tissues (ANCT) and metastatic lymph node (MLN) tissues were collected. The expression of RAGE and EGR1 was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of RAGE in GAC and MLN tissues showed the positive staining mainly in the cytoplasm, with lower reactivity rate compared with the ANCT (P less than 0.001), while EGR1 expression had no significant difference between GAC, MLN tissues and ANCT (P=0.565). Moreover, the positive expression of RAGE was closely associated with the N stage of GAC patients, but did not correlate with their age, gender, tumor size, tumor sites, T stage, and metastatic lymph node (each P>0.05). In addition, Spearman Rank correlation analysis showed the positive correlation of RAGE expression with EGR1 in GAC tissues (r=0.658). Taken together, the expression of RAGE is decreased in GAC and MLN tissues, and is associated with the N stage of GAC patients, suggesting that RAGE may represent a potential therapeutic target for the treatment of GAC.

BACKGROUND/AIMS: Amphoterin is considered as a regulator for the ability of invasion and migration in tumor cells and embryonic neurons through binding to receptor for advanced glycation end products (RAGE), a multiligand cell surface molecule of the immunoglobulin superfamily. As matrix metalloproteinase-9 (MMP-9, gelatinase B) has been reported to play a critical role in tumor progression and metastasis, we have examined the relation of RAGE and MMP in human pancreatic cancer. METHODOLOGY: Three representative human pancreatic carcinoma cells were rendered for the study which show different metastatic potential, PANC-1 and MIA PaCa-2 as the cells with high ability, BxPC-3 as with low. The expression of RAGE was examined by RT-PCR. The expression of MMP-9 protein was examined by Western blotting. RESULTS: RAGE was strongly expressed in MIA PaCa-2 and PANC-1 that have high metastatic ability. On the contrary, RAGE was expressed little in BxPC-3 that has low ability. Similarly, expression of MMP-9 showed almost the same tendency. RAGE and MMP-9 are expressed concordant with the metastatic ability of the human pancreatic cancer cells. CONCLUSIONS: Control of these molecules could be a key to regulating the metastatic ability of pancreatic cancer and this may be exploited in targeted therapy of this cancer.