ArticleGastroenterology2010
Reg IV regulates normal intestinal and colorectal cancer cell susceptibility to radiation-induced apoptosis.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.World journal of gastroenterology · 2023Pooled it
- Overexpression of regenerating islet-derived type 4 isoform 2 increases colorectal cancer cell proliferation.Biochemistry and biophysics reports · 2026Article
- REG/Reg family proteins: mediating gut microbiota homeostasis and implications in digestive diseases.Gut microbes · 2025Review
- The Reg gene family: roles in gastric and colorectal cancer progression and its potential for targeted therapy.Discover oncology · 2025Review
- REG4 promotes the proliferation and anti-apoptosis of cancer.Frontiers in cell and developmental biology · 2022Review
- Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer.Medicina (Kaunas, Lithuania) · 2021Article
- The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract.International journal of molecular sciences · 2021Review
- Reg4 and its downstream transcriptional activator CD44ICD in stage II and III colorectal cancer.Oncotarget · 2021Article
- The Clinical Significance and Mechanisms of REG4 in Human Cancers.Frontiers in oncology · 2020Review
- The Link between Type III Reg and STAT3-Associated Cytokines in Inflamed Colonic Tissues.Mediators of inflammation · 2019Article
- Regenerating Family Member 4 (Reg4) Enhances 5-Fluorouracil Resistance of Gastric Cancer Through Activating MAPK/Erk/Bim Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Recombinant Reg3β protein protects against streptozotocin-induced β-cell damage and diabetes.Scientific reports · 2016Article
- REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.Scientific reports · 2015Article
- The role of the REG4 gene and its encoding product in ovarian epithelial carcinoma.BMC cancer · 2015Article
- The role of Reg IV in colorectal cancer, as a potential therapeutic target.Contemporary oncology (Poznan, Poland) · 2015Review
- Helminth infections decrease host susceptibility to immune-mediated diseases.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Reg4-induced mitogenesis involves Akt-GSK3β-β-Catenin-TCF-4 signaling in human colorectal cancer.Molecular carcinogenesis · 2014Article
- RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers.PloS one · 2014Article
- Article
- Enhanced RegIV expression predicts the intrinsic 5-fluorouracil (5-FU) resistance in advanced gastric cancer.Digestive diseases and sciences · 2013Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsRegenerating (Reg) gene IV is predominantly expressed in gastrointestinal cells and highly up-regulated in many gastrointestinal malignancies, including colorectal cancer (CRC). Human CRC cells expressing higher levels of Reg IV gene and its protein product (Reg IV) are resistant to conventional therapies, including irradiation (IR). However, the underlying mechanism is not well defined.
methodsA murine model of IR-induced intestinal injury and in vitro and in vivo models of human CRC were used to determine the role of Reg IV in regulation of normal intestinal and colorectal cancer cell susceptibility to IR-induced apoptosis.
resultsTreatments of recombinant human Reg IV (rhR4) protein protected normal intestinal crypt cells from IR-induced apoptosis by increasing the expression of antiapoptotic genes Bcl-2, Bcl-XL, and survivin. However, overexpression of Reg IV in human CRC cells was associated with increased resistance to IR-induced apoptosis. Therefore, we used antagonism of Reg IV as a tool to increase CRC cell susceptibility to IR-induced cell death. Two complementary approaches using specific monoclonal antibodies and small interfering RNAs were tested in both in vitro and in vivo models of human CRC. Both approaches resulted in increased apoptosis and decreased cell proliferation, leading to decreased tumor growth and increased animal survival. Furthermore, these approaches increased CRC cell susceptibility to IR-induced apoptosis.
conclusionsThese results implicate Reg IV as an important modulator of gastrointestinal cell susceptibility to IR; hence, it is a potential target for adjunctive treatments for human CRC and other gastrointestinal malignancies.
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Registered trials
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