ArticlePloS one2013
Silencing of RASSF3 by DNA hypermethylation is associated with tumorigenesis in somatotroph adenomas.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- DNA Methylation in Pituitary Adenomas: A Scoping Review.International journal of molecular sciences · 2025Article
- Regulation of RASSF by non-coding RNAs in different cancers: RASSFs as masterminds of their own destiny as tumor suppressors and oncogenes.Non-coding RNA research · 2022Review
- Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors.Biomedicines · 2020Review
- Pumping the brakes on RAS - negative regulators and death effectors of RAS.Journal of cell science · 2020Review
- The Role and Function of Ras-association domain family in Cancer: A Review.Genes & diseases · 2019Review
- Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism.Genome biology · 2017Article
- Ras signaling through RASSF proteins.Seminars in cell & developmental biology · 2016Review
- Animal models of pituitary neoplasia.Molecular and cellular endocrinology · 2016Review
- Promoter methylation status of Ras-association domain family members in pheochromocytoma.Frontiers in endocrinology · 2015Article
- Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma.Molecular and cellular endocrinology · 2014Review
- The role of genetic and epigenetic changes in pituitary tumorigenesis.Neurologia medico-chirurgica · 2014Review
Corrections and comments
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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
The pathogenic mechanisms underlying pituitary somatotroph adenoma formation, progression are poorly understood. To identify candidate tumor suppressor genes involved in pituitary somatotroph adenoma tumorigenesis, we used HG18 CpG plus Promoter Microarray in 27 human somatotroph adenomas and 4 normal human adenohypophyses. RASSF3 was found with frequent methylation of CpG island in its promoter region in somatotroph adenomas but rarely in adenohypophyses. This result was confirmed by pyrosequencing analysis. We also found that RASSF3 mRNA level correlated negatively to its gene promoter methylation level. RASSF3 hypermethylation and downregulation was also observed in rat GH3 and mouse GT1.1 somatotroph adenoma cell lines. 5-Aza-2' deoxycytidine and trichostatin-A treatment induced RASSF3 promoter demethylation, and restored its expression in GH3 and GT1.1 cell lines. RASSF3 overexpression in GH3 and GT1.1 cells inhibited proliferation, induced apoptosis accompanied by increased Bax, p53, and caspase-3 protein and decreased Bcl-2 protein expression. We also found that the antitumor effect of RASSF3 was p53 dependent, and p53 knockdown blocked RASSF3-induced apoptosis and growth inhibition. Taken together, our results suggest that hypermethylation-induced RASSF3 silencing plays an important role in the tumorigenesis of pituitary somatotroph adenomas.
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