Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subclassification of intraductal papillary mucinous neoplasms of the pancreas (IPMNs), based on morphological features and immunohistochemical profiles, has been proposed. Intestinal-type IPMNs frequently show moderate to severe dysplasia. Regenerating islet-derived family, member 4 (REG4) is associated with the adenoma-carcinoma sequence in colon cancer and it is also associated with intestinal phenotype. Therefore, to identify REG4 expression in IPMNs may be helpful to detect high-grade IPMNs. We also investigated REG4 expression and CDX2 expression in IPMNs. To investigate the expressions of REG4 and CDX2 in IPMNs and in invasive ductal adenocarcinoma derived from IPMN, we used immunohistochemical staining and microdissection-based quantitative real-time reverse transcription-polymerase chain reaction. Among 125 IPMNs, 43 (34%) were positive for REG4 and most of the intestinal-type IPMNs showed its expression (35/38). The positive ratio of REG4 expression in colloid carcinoma (5/7) was significantly higher than that in tubular carcinoma (1/17; P=0.003). Most of CDX2-positive cases (31/33) expressed REG4 protein, whereas only 12 of 92 CDX2-negative cases did (P<0.001). The levels of REG4 mRNA in intestinal-type IPMN were significantly higher compared to those in gastric-type IPMN or to normal pancreatic ductal epithelium (P=0.005, P=0.004, respectively). REG4 expression was observed more frequently in borderline lesions (14/28) and carcinoma (21/45) compared to adenoma (8/52). Using the Ki-67 labeling index, REG4 expression was significantly correlated with proliferative activity in borderline lesions. We conclude that REG4 is involved in the 'intestinal' pathway of carcinogenesis in IPMN.
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PMID:REG4 is associated with carcinogenesis in the 'intestinal' pathway of intraductal papillary mucinous neoplasms. 1913 34

Regenerating islet-derived family, member 4 (Reg IV) has been shown to be associated with colorectal carcinogenesis and gastric carcinogenesis through intestinal metaplasia. In this study, we examined Reg IV expression in the gallbladder and gallbladder carcinoma, and measured Reg IV levels in sera from patients with gallbladder carcinoma. Quantitative reverse transcription-polymerase chain reaction revealed that high Reg IV levels were identified in 17 of 31 gallbladder carcinomas, whereas there was no apparent amplification in normal gallbladders. Immunohistochemically, although only a small part of the epithelium with intestinal metaplasia in 2 of 4 cases with adenomyomatosis showed Reg IV expression, Reg IV was negative in all cases with normal gallbladder (n = 15) and cholelithiasis (n = 13). In contrast, 34 (56%) of 61 gallbladder carcinomas were positive. Expression was more frequently observed in well to moderately differentiated than in poorly differentiated adenocarcinomas and significantly correlated with expression of caudal-related homeobox transcription factor (a candidate for involvement in the induction of intestinal metaplasia). Multivariate analysis revealed negative Reg IV expression, as well as hepatic parenchymal invasion, to be independently associated with a poor prognosis in patients with advanced gallbladder carcinoma. Before surgical resection, 4 (33%) of 12 patients with gallbladder carcinoma had high serum Reg IV levels, whereas Reg IV was never elevated in 12 patients with benign diseases. The serum levels of Reg IV decreased after surgical resection of the tumors. These results suggest that Reg IV is involved in gallbladder carcinoma carcinogenesis through intestinal metaplasia and is associated with relatively favorable prognosis in patients after surgery. The serum level of Reg IV may be of use or indicative of neoplasia.
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PMID:Reg IV expression and clinicopathologic features of gallbladder carcinoma. 1971 64

Regenerating islet-derived family, member 4 (Reg IV), a member of the Reg gene family, has been reported to be overexpressed in gastrointestinal tract cancers. Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis. Reg IV activates the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer and increases expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), which are associated with the inhibition of apoptosis, results in mitogenic signaling in colon cancer cells, increase cell proliferation, metastasis and decreased apoptosis. Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD). These studies may lead to novel therapeutic strategies for cancers expressing Reg IV. Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect. This review summaries current knowledge of the expression and roles of Reg IV in human colorectal cancer, describes the possible signaling pathway which Reg IV activates, and discusses the relevance of Reg IV as a potential therapeutic target for cancer treatment.
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PMID:The role of Reg IV in colorectal cancer, as a potential therapeutic target. 2655 71