Expression of regenerating gene I in gastric adenocarcinomas

Dhar, Dipok Kumar; Udagawa, Jun; Ishihara, Shunji; Otani, Hiroki; Kinoshita, Yoshikazu; Takasawa, Shin; Okamoto, Hiroshi; Kubota, Hirofumi; Fujii, Toshiyuki; Tachibana, Mitsuo; Nagasue, Naofumi

doi:10.1002/cncr.20097

Cited by 49 publications

(18 citation statements)

References 29 publications

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“…In gastric and colorectal tumors, the expression of this gene is closely correlated to carcinoma invasiveness (Macadam et al, 2000;Dhar et al, 2004). Whether expression of REG1A and REG3A during hepatocarcinogenesis is a marker of poor prognosis is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with β-catenin mutations

et al. 2005

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The Wnt/b-catenin signaling pathway is activated in many human hepatocellular carcinomas (HCC). We tried to identify the genes involved in carcinogenesis and progression of HCC with b-catenin mutations. We used PCRbased subtractive hybridization to compare gene expression between malignant and benign components of a human HCC occurring in pre-existing adenoma activated for b-catenin. Two of the genes identified belong to the Regenerating gene (REG) family. They encode the Regenerating islet-derived 3 alpha (REG3A/HIP/PAP/ REG-III) and 1 alpha (REG1A) proteins, both involved in liver and pancreatic regeneration and proliferation. Using siRNA directed against b-catenin, we demonstrated that REG3A is a target of b-catenin signaling in Huh7 hepatoma cells. The upregulation of REG3A and REG1A expression is significantly correlated to the b-catenin status in 42 HCC and 28 hepatoblastomas characterized for their b-catenin status. Thus, we report strong evidence that both genes are downstream targets of the Wnt pathway during liver tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with β-catenin mutations

et al. 2005

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“…Reg IV is a member of the Reg gene family, which includes three other genes (Reg Iα, Reg Iβ and Reg III) [7]. In GC, expression of Reg Iα has been reported [8, 9]. Reg Iα expression is enhanced in advanced T grade GCs and in GCs that were not well differentiated.…”

Section: Introductionmentioning

confidence: 99%

Serum Concentration of Reg IV in Patients with Colorectal Cancer: Overexpression and High Serum Levels of Reg IV Are Associated with Liver Metastasis

Oue¹,

Kuniyasu

Noguchi

et al. 2007

Oncology

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Objective: Regenerating islet-derived family, member 4 (regenerating gene type IV, Reg IV) is overexpressed in colorectal cancer (CRC). The aim of this study was to investigate the diagnostic utility of Reg IV determination in sera from patients with CRC. Methods: We examined the expression and distribution of Reg IV in CRC by immunohistochemistry and determined Reg IV levels in sera from patients with CRC by enzyme-linked immunosorbent assay. Results: Immunostaining revealed that 23 of 80 (29%) CRC cases were positive for Reg IV. CRC cases with metastatic recurrence in the liver showed more frequently Reg IV staining than those without (p = 0.0102). Patients with CRC showing Reg IV staining had a significantly worse survival than those without Reg IV staining (p = 0.0117). Preoperatively, serum Reg IV concentrations were not elevated in CRC patients at stage 0–III, being in contrast to the significantly increased preoperative levels in stage IV CRC patients with liver metastasis. Conclusion: These results suggest that Reg IV is a prognosticator for poor survival. Serum Reg IV concentration may predict CRC recurrence in the liver.

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“…Because Reg family members have highly similar structures, we initially examined whether the ELISA system cross-reacted with other family members such as Reg-Iα, -Iβ, and -IV, whose expressions were previously reported in some malignant tissues. [13,16,18-20] The ELISA system detected only HIP/PAP and had no or almost negligible cross-reactivity with other human family members (Figure2). As shown in Figure3A, the urinary HIP/PAP concentration in the BCa group was significantly higher than that in controls (median value; 3.184 pg/mL vs. 55.200 pg/mL, P < 0.0001).…”

Section: Resultsmentioning

confidence: 99%

Urinary levels of Hepatocarcinoma-intestine-pancreas/Pancreatitis-associated protein as a diagnostic biomarker in patients with bladder cancer

et al. 2012

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BackgroundTo assess the possibility of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) as a biological marker for detecting Bladder cancer (BCa), we examined the expression of HIP/PAP in both BCa specimens and BCa cell lines and measured HIP/PAP levels in urine from patients with BCa.MethodsHIP/PAP expression in BCa samples was evaluated by western blot analysis, and urinary levels of HIP/PAP in patients with BCa were measured by enzyme-linked immunosorbent assay. Urine samples were collected from 10 healthy volunteers and 109 with benign urological disorders as controls, and from 101 patients who were diagnosed with BCa.ResultsHIP/PAP was highly expressed in BCa samples as compared with control bladder. Urinary HIP/PAP concentrations were significantly higher in BCa patients than in controls (median value; 3.184 pg/mL vs. 55.200 pg/mL, P <0.0001, by Mann–Whitney U test). Urinary HIP/PAP levels in BCa patients correlated positively with pathological T stages and progression-risk groups among non-muscle invasive BCa (P = 0.0008, by Kruskal-Wallis test). Regarding the recurrence-risk classifications of non-muscle invasive BCa, the urinary levels of HIP/PAP were significantly higher in the intermediate than in the low risk group (P = 0.0002, by Mann–Whitney U test). Based on a cut-off of 8.5 pg/mL, the ability of urinary HIP/PAP levels to detect BCa had a sensitivity of 80.2%, specificity of 78.2%, positive predictive value (PPV) of 75.7%, and negative predictive value (NPV) of 82.3%.ConclusionsHIP/PAP was abundantly expressed in BCa, and the urinary levels of HIP/PAP could be a novel and potent biomarker for detection of BCa, and also for predicting the risks of recurrence- and progression-risk of non-muscle invasive BCa. A large scale study will be needed to establish the usefulness of this biomarker.

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Expression of regenerating gene I in gastric adenocarcinomas

Cited by 49 publications

References 29 publications

Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with β-catenin mutations

Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with β-catenin mutations

Serum Concentration of Reg IV in Patients with Colorectal Cancer: Overexpression and High Serum Levels of Reg IV Are Associated with Liver Metastasis

Urinary levels of Hepatocarcinoma-intestine-pancreas/Pancreatitis-associated protein as a diagnostic biomarker in patients with bladder cancer

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