Trial reportThe Journal of biological chemistry2012
Impaired transforming growth factor-β (TGF-β) transcriptional activity and cell proliferation control of a menin in-frame deletion mutant associated with multiple endocrine neoplasia type 1 (MEN1).
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- Two novel multiple endocrine neoplasia type 1 variants caused thymic neuroendocrine tumor: a case report.Hereditary cancer in clinical practice · 2026Article
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- Article
- Deep Learning Techniques to Characterize theBiomedicines · 2024Article
- Challenges in molecular diagnosis of multiple endocrine neoplasia.Frontiers in endocrinology · 2024Review
- Alternative splicing generates isoform diversity inEndocrine oncology (Bristol, England) · 2024Article
- Clinical and molecular features of four Brazilian families with multiple endocrine neoplasia type 1.Frontiers in endocrinology · 2023Article
- Effect of Menin Deletion in Early Osteoblast Lineage on the Mineralization of an In Vitro 3D Osteoid-like Dense Collagen Gel Matrix.Biomimetics (Basel, Switzerland) · 2022Article
- Unusual Combination of MEN-1 and the Contiguous Gene Deletion Syndrome of CAH and Ehlers-Danlos Syndrome (CAH-X).Journal of the Endocrine Society · 2020Article
- Evolution of Our Understanding of the Hyperparathyroid Syndromes: A Historical Perspective.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Review
- Molecular Genetic Studies of Pancreatic Neuroendocrine Tumors: New Therapeutic Approaches.Endocrinology and metabolism clinics of North America · 2018Review
- Current and emerging therapies for PNETs in patients with or without MEN1.Nature reviews. Endocrinology · 2018Review
- Epigenetic regulation by the menin pathway.Endocrine-related cancer · 2017Review
- Novel association ofOncology letters · 2017Article
- Novel MEN 1 gene findings in rare sporadic insulinoma--a case control study.BMC endocrine disorders · 2015Article
- Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion.The application of clinical genetics · 2015Article
- Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma.Molecular and cellular endocrinology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Multiple endocrine neoplasia type 1 (MEN1) is characterized by tumors of the parathyroid, enteropancreas, and anterior pituitary. The MEN1 gene encodes the tumor suppressor menin of 610 amino acids that has multiple protein partners and activities. The particular pathways that, when lost, lead to tumorigenesis are not known. We demonstrated that members of a three-generation MEN1 kindred are heterozygous for a donor splice site mutation at the beginning of intron 3 (IVS3 + 1G→A). Lymphoblastoid cells of a mutant gene carrier had, in addition to the wild-type menin transcript, an aberrant transcript resulting from use of a cryptic splice site within exon III that splices to the start of exon IV. The predicted menin Δ(184-218) mutant has an in-frame deletion of 35 amino acids but is otherwise of wild-type sequence. The transfected menin Δ(184-218) mutant was well expressed and fully able to mediate the normal inhibition of the activity of the transcriptional regulators JunD and NF-κB. However, it was defective in mediating TGF-β-stimulated Smad3 action in promoter-reporter assays in insulinoma cells. Importantly, lymphoblastoid cells from an individual heterozygous for the mutation had reduced TGF-β-induced (Smad3) transcriptional activity but normal JunD and NF-κB function. In addition, the mutant gene carrier lymphoblastoid cells proliferated faster and were less responsive to the cytostatic effects of TGF-β than cells from an unaffected family member. In conclusion, the menin mutant exhibits selective loss of the TGF-β signaling pathway and loss of cell proliferation control contributing to the development of MEN1.
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What OpenQuestion holds
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.