Disease relevance of RPRM

• Loss of Reprimo gene expression accompanied by its promoter methylation was identified in pancreatic and lung cancers [1].
• Furthermore, we failed to identify Reprimo mutation in colorectal and gastric cancer cell lines and 50 primary colorectal cancers [1].
• RESULTS: In Barrett's esophagus (BE; P = 0.001), high-grade dysplasia (HGD; P = 0.001), and esophageal adenocarcinoma (EAC; P = 0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE) [2].
• PURPOSE: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G(2) phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer [2].
• The biological and clinical relevance of Reprimo methylation in pancreatic cancer was investigated [3].

High impact information on RPRM

• Thus, Reprimo may be a new member involved in the regulation of p53-dependent G(2) arrest of the cell cycle [4].
• Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase [4].
• Reprimo Methylation Is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression [2].
• CONCLUSIONS: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia [2].
• We examined Reprimo expression by RT-PCR and the DNA methylation status of the Reprimo promoter by MSP in 39 tumor cell lines [1].

Biological context of RPRM

• Reprimo is a highly glycosylated protein and, when ectopically expressed, it is localized in the cytoplasm and induces G(2) arrest of the cell cycle [4].
• Aberrant methylation of Reprimo in human malignancies [1].
• Loss or downregulation of Reprimo expression was frequent (62%), and we confirmed that transcriptional repression of Reprimo was caused by hypermethylation (overall concordance 92%) [1].
• We examined Reprimo expression by reverse transcription PCR (RT-PCR) and aberrant methylation of Reprimo by methylation specific PCR (MSP) in lung cancer cell lines (n=35) and primary tumors (n=167) [5].
• Copper treatment resulted in the upregulation of p21, reprimo, stathmin, and Tp53INP1, all known to participate in cell cycle arrest [6].

Anatomical context of RPRM

• Promoter methylation of Reprimo was found in 79% of gastric cancers, 62% of gallbladder cancers, 57% of lymphomas, 56% of colorectal cancers, 40% of esophageal adenocarcinomas, 37% of breast cancers and 31% of leukemias [1].

Associations of RPRM with chemical compounds

• Treatment of expression-negative cells with 5-aza-2'-deoxycytidine restored Reprimo expression [1].

Other interactions of RPRM

• Reprimo is a new candidate mediator of p53-mediated cell cycle arrest at the G2 phase [1].
• Reprimo, a gene involved in the p53-induced G2 cell cycle arrest, has been recently identified as a novel target for aberrant methylation in pancreatic and other cancers [3].
• METHODS: The methylation status of Reprimo CpG island was analyzed by methylation-specific polymerase chain reaction in a large series of pancreatic cancers and was correlated with p53 mutation status, genetic instability (as measured by the fractional allelic loss), and clinicopathologic features [3].

Analytical, diagnostic and therapeutic context of RPRM

• EXPERIMENTAL DESIGN: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens [2].
• RESULTS: Aberrant methylation of Reprimo was identified in 60% (75 of 125) of pancreatic cancer xenografts and primary pancreatic adenocarcinomas [3].
• Reprimo expression was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine in all five-cell lines tested that lacked Reprimo expression [5].

References