ArticleThe American journal of pathology2015
Loss of Lrig1 leads to expansion of Brunner glands followed by duodenal adenomas with gastric metaplasia.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions.Nature communications · 2025Article
- Regenerative Role of Lrig1+ Cells in Kidney Repair.Journal of the American Society of Nephrology : JASN · 2024Article
- KRAS G12D mutation in Brunner gland adenoma.BMJ case reports · 2023Article
- HYPOTHESIS: Do LRIG Proteins Regulate Stem Cell Quiescence by Promoting BMP Signaling?Stem cell reviews and reports · 2023Review
- Aberrant promoter methylation contributes to LRIG1 silencing in basal/triple-negative breast cancer.British journal of cancer · 2022Article
- Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells.Cell stem cell · 2022Article
- Gastrin: From Physiology to Gastrointestinal Malignancies.Function (Oxford, England) · 2022Review
- Cell-Autonomous Role of EGFR in Spontaneous Duodenal Tumors in LRIG1 Null Mice.Cellular and molecular gastroenterology and hepatology · 2021Article
- A smooth muscle-derived, Braf-driven mouse model of gastrointestinal stromal tumor (GIST): evidence for an alternative GIST cell-of-origin.The Journal of pathology · 2020Article
- Identification and Characterization of Unique Neutralizing Antibodies to Mouse EGF Receptor.Gastroenterology · 2020Article
- Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress.Cell stem cell · 2019Article
- LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer.Nature communications · 2019Article
- Transfer of Functional Cargo in Exomeres.Cell reports · 2019Article
- Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis.The American journal of pathology · 2018Article
- Article
- HDAC-4 regulates claudin-2 expression in EGFR-ERK1/2 dependent manner to regulate colonic epithelial cell differentiation.Oncotarget · 2017Article
- Pathophysiology of Gastric NETs: Role of Gastrin and Menin.Current gastroenterology reports · 2017Review
- Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells.The Biochemical journal · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-ErbB negative regulator and intestinal stem cell marker down-regulated in many malignancies. We previously reported that 14 of 16 Lrig1-CreERT2/CreERT2 (Lrig1(-/-)) mice developed duodenal adenomas, providing the first in vivo evidence that Lrig1 acts as a tumor suppressor. We extended this study to a larger cohort and found that 49 of 54 Lrig1(-/-) mice develop duodenal adenomas beginning at 3 months. Most adenomas were histologically low grade and overlaid expanded Brunner glands. There was morphologic and biochemical blurring of the boundary between the epithelium and Brunner glands with glandular coexpression of ErbB2, which is normally restricted to the epithelium, and the Brunner gland marker Mucin6. Some adenomas were high grade with reduced Brunner glands. At age 4 to 5 weeks, before adenoma formation, we observed enhanced proliferation in Brunner glands and, at 2 months, an increase in the size of the Brunner gland compartment. Elevated expression of the epidermal growth factor receptor (Egfr) ligands amphiregulin and β-cellulin, as well as Egfr and phosphorylated Egfr, was detected in adenomas compared with adjacent normal tissue. These adenomas expressed the gastric-specific genes gastrokine1 and mucin5ac, indicating gastric metaplasia. Moreover, we found that a subset of human duodenal tumors exhibited features of LRIG1(-/-) adenomas, including loss of LRIG1, gastric metaplasia (MUCIN5AC and MUCIN6), and increased amphiregulin and Egfr activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.