ArticlePloS one2011
Loss of glucocorticoid receptor expression by DNA methylation prevents glucocorticoid induced apoptosis in human small cell lung cancer cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.
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.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.EBioMedicine · 2017Pooled it
- Maternal-infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age.American journal of human biology : the official journal of the Human Biology Council · 2023Article
- Glucocorticoid mediated inhibition of LKB1 mutant non-small cell lung cancers.Frontiers in oncology · 2023Article
- Phosphodiesterase 5 inhibitor mirodenafil ameliorates Alzheimer-like pathology and symptoms by multimodal actions.Alzheimer's research & therapy · 2022Article
- Review
- Long non-coding RNA growth arrest specific-5: a potential biomarker for early diagnosis of severe asthma.Journal of thoracic disease · 2020Article
- Lung Cancer Screening and Epigenetics in African Americans: The Role of the Socioecological Framework.Frontiers in oncology · 2019Article
- A General Introduction to Glucocorticoid Biology.Frontiers in immunology · 2019Review
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
- Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD.ACS chemical biology · 2018Article
- The tobacco carcinogen NNK drives accumulation of DNMT1 at the GR promoter thereby reducing GR expression in untransformed lung fibroblasts.Scientific reports · 2018Article
- DNA residence time is a regulatory factor of transcription repression.Nucleic acids research · 2017Article
- The effects of microRNAs on glucocorticoid responsiveness.Journal of cancer research and clinical oncology · 2017Review
- Childhood abuse, promoter methylation of leukocyte NR3C1 and the potential modifying effect of emotional support.Epigenomics · 2016Article
- Epigenetic and Glucocorticoid Receptor-Mediated Regulation of Glutathione Peroxidase 3 in Lung Cancer Cells.Molecules and cells · 2016Article
- Article
- Hypermethylation of glucocorticoid receptor gene promoter results in glucocorticoid receptor gene low expression in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.Rheumatology international · 2015Article
- Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Frequent promoter hypermethylation and expression reduction of the glucocorticoid receptor gene in breast tumors.Epigenetics · 2014Article
- Bim polymorphisms: influence on function and response to treatment in children with acute lymphoblastic leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Human small cell lung cancer (SCLC) is highly aggressive, and quickly develops resistance to therapy. SCLC cells are typically insensitive to glucocorticoids due to impaired glucocorticoid receptor (GR) expression. This is important as we have previously shown that expression of a GR transgene induces cell death in-vitro, and inhibits tumor growth in-vivo. However, the underlying mechanism for loss of GR expression is unknown. The SCLC cell line, DMS79, has low GR expression, compared to non-SCLC cell lines and normal bronchial epithelial cells. Retroviral GR expression in DMS79 cells caused activation of the apoptotic pathway as evidenced by marked induction of caspase-3 activity. Methylation analysis of the GR promoter revealed some methylation in the 1D, and 1E promoters of the GR gene, however the ubiquitous constitutively active 1C promoter was heavily methylated. In the 1C promoter there was a highly significant increase in DNA methylation in a panel of 14 human SCLC cell lines compared to a mixed panel of GR expressing, and non-expressing cell lines, and to peripheral blood mononuclear cells. Furthermore, within the panel of SCLC cell lines there was a significant negative correlation seen between methylation of the 1C promoter, and GR protein expression. Reversal of GR gene methylation with DNA methyltransferase inhibition caused increased GR mRNA and protein expression in SCLC but not non-SCLC cells. This resulted in increased Gc sensitivity, decreased Bcl-2 expression and increased caspase-3 activity in SCLC cells. These data suggest that DNA methylation decreases GR gene expression in human SCLC cells, in a similar manner to that for conventional tumor suppressor genes.
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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.