ArticleMolecular and cellular biology1991
A position-dependent silencer plays a major role in repressing alpha-fetoprotein expression in human hepatoma.
Article in Molecular and cellular biology, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 147 citations in OpenAlex.
- Alpha-Fetoprotein as a Biomarker in Pregnancy: From Genetic Disorders to Obstetric Complications.Current issues in molecular biology · 2026Review
- Alpha fetoprotein (AFP)-producing gastric cancer: clinicopathological features and treatment strategies.Cell & bioscience · 2025Review
- The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?International journal of biological sciences · 2022Review
- Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma.BMC cancer · 2021Article
- Analysis of endogenous and exogenous tumor upregulated promoter expression in canine tumors.PloS one · 2020Article
- Observational
- Genetic correction of serum AFP level improves risk prediction of primary hepatocellular carcinoma in the Dongfeng-Tongji cohort study.Cancer medicine · 2018Article
- Hepatocellular carcinoma-targeting oncolytic adenovirus overcomes hypoxic tumor microenvironment and effectively disperses through both central and peripheral tumor regions.Scientific reports · 2018Article
- Genetic correction improves prediction efficiency of serum tumor biomarkers on digestive cancer risk in the elderly Chinese cohort study.Oncotarget · 2018Article
- Persistent α-Fetoprotein Elevation in Healthy Adults and Mutational Analysis of α-Fetoprotein Promoter, Enhancer, and Silencer Regions.Gut and liver · 2017Article
- TGF- β Signaling Cooperates with AT Motif-Binding Factor-1 for Repression of the α -Fetoprotein Promoter.Journal of signal transduction · 2014Article
- Hypoxia/hepatoma dual specific suicide gene expression plasmid delivery using bio-reducible polymer for hepatocellular carcinoma therapy.Journal of controlled release : official journal of the Controlled Release Society · 2013Article
- Article
- Complete eradication of hepatomas using an oncolytic adenovirus containing AFP promoter controlling E1A and an E1B deletion to drive IL-24 expression.Cancer gene therapy · 2012Article
- Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL.Cancer gene therapy · 2012Article
- Cancer targeting Gene-Viro-Therapy of liver carcinoma by dual-regulated oncolytic adenovirus armed with TRAIL gene.Gene therapy · 2011Article
- Article
- Applications of RNA interference in cancer therapeutics as a powerful tool for suppressing gene expression.Molecular biology reports · 2009Review
- Transformation of human liver L-O2 cells mediated by stable HBx transfection.Acta pharmacologica Sinica · 2009Article
- A tumor-specific conditionally replicative adenovirus vector expressing TRAIL for gene therapy of hepatocellular carcinoma.Cancer gene therapy · 2006Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A large percentage of human hepatomas produce alpha-fetoprotein (AFP), but the levels of AFP expression vary greatly among hepatomas. To understand the molecular basis for this variation, we analyzed transcriptional regulatory activities associated with the 5'-flanking region of the AFP gene in two human hepatoma cell lines, HuH-7 and huH-1/cl-2, which produce a high and a low level of AFP, respectively. We found that the low level of AFP production in huH-1/cl-2 is due to the action of at least two silencer regions located between the enhancer and the promoter of the AFP gene. In contrast, no silencer activity is expressed in HuH-7. We identified 5'-CTTCATAACTAATACTT-3' to be a core sequence responsible for the negative regulatory activity. This sequence is repeated four times in a strong, distal silencer region, Sd, whereas one copy is present in a weak, proximal silencer region, Sp. The silencer reduces transcriptional initiation by blocking enhancer activation of the AFP promoter in a position-dependent manner. The silencer functions in the presence of positive transcription factors and may play a key role in developmental repression as well as variable expression of the AFP gene in hepatomas.
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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.