ArticleOncogene2004
Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation.
Article in Oncogene, 2004. 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, 98 citations in OpenAlex.
- Current understanding of the role of DNA methylation in pituitary neuroendocrine tumors.Neuro-oncology advances · 2025Article
- A Brief Overview of Molecular Biology in Pituitary Adenomas with a Focus on Aggressive Lesions.International journal of molecular sciences · 2025Review
- DNA Methylation in Pituitary Adenomas: A Scoping Review.International journal of molecular sciences · 2025Article
- The evolution and application of multi-omic analysis for pituitary neuroendocrine tumors.Frontiers in medicine · 2025Review
- Roles for GADD45 in Development and Cancer.Advances in experimental medicine and biology · 2022Review
- Single-cell transcriptome and genome analyses of pituitary neuroendocrine tumors.Neuro-oncology · 2021Article
- Article
- Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?Endocrine pathology · 2021Review
- Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors.Biomedicines · 2020Review
- GADD45G Interacts with E-cadherin to Suppress the Migration and Invasion of Esophageal Squamous Cell Carcinoma.Digestive diseases and sciences · 2020Article
- Genetic and Epigenetic Causes of Pituitary Adenomas.Frontiers in endocrinology · 2020Review
- The Epigenomics of Pituitary Adenoma.Frontiers in endocrinology · 2019Review
- Overexpression of DNA (Cytosine-5)-Methyltransferase 1 (DNMT1) And DNA (Cytosine-5)-Methyltransferase 3A (DNMT3A) Is Associated with Aggressive Behavior and Hypermethylation of Tumor Suppressor Genes in Human Pituitary Adenomas.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Bioinformatic analysis of gene expression profiles of pituitary gonadotroph adenomas.Oncology letters · 2018Article
- Article
- Methylation mediated Gadd45β enhanced the chemosensitivity of hepatocellular carcinoma by inhibiting the stemness of liver cancer cells.Cell & bioscience · 2017Article
- Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?Turkish journal of haematology : official journal of Turkish Society of Haematology · 2015Article
- Identification of differentially expressed genes in pituitary adenomas by integrating analysis of microarray data.International journal of endocrinology · 2015Article
- Genomic approaches to problems in pituitary neoplasia.Endocrine pathology · 2014Review
- Clocks for all seasons: unwinding the roles and mechanisms of circadian and interval timers in the hypothalamus and pituitary.The Journal of endocrinology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inappropriate expression of cell-cycle regulatory genes and/or their protein products are a frequent finding in pituitary tumours; however, genetic changes associated with or responsible for their dysregulation are in general uncommon. In a search for novel genes, and employing cDNA-representational difference analysis, the gene encoding GADD45gamma was recently isolated and identified as being under-represented in pituitary adenomas. GADD45gamma is a member of a family of genes that are induced by DNA damage and function in the negative regulation of cell growth. In this study, we further confirm this initial report that the majority of pituitary adenomas (22 of 33; 67%) do not express GADD45gamma as determined by RT-PCR analysis. Loss of expression was not associated with either loss of heterozygosity or mutations within the coding region of this gene. In marked contrast, epigenetic change, namely methylation of the GADD45gamma genes CpG island, was a frequent finding (19 of 33 adenoma; 58%) and was significantly associated with tumours in which GADD45gamma transcript was not expressed (18 of 22; 82%; P=0.002). In common with the primary tumours, methylation-associated gene silencing of the GADD45gamma gene was also found in the pituitary tumour cell line AtT20. The treatment of AtT20 cells with the demethylating agent, 5-Aza-2'-deoxycytidine, induced the re-expression of this gene. These findings show that silencing of the GADD45gamma gene in pituitary tumours is primarily associated with methylation of the genes CpG island. Methylation has functional importance since reversal of this epigenetic change in a pituitary-derived cell line is associated with re-expression. Silencing of GADD45gamma, a negative regulator of cell growth, is most likely responsible for conferring a selective growth advantage during tumour evolution and outgrowth.
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