Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abrogation of cellular senescence, resulting in immortalization, is a necessary step in the tumorigenic transformation of a cell. Four independent, spontaneously immortalized Li-Fraumeni syndrome (LFS) cell lines were used to analyze the gene expression changes that may have given these cell lines the growth advantage required to become immortal. A cellular senescence-like phenotype can be induced in immortal LFS cells by treating them with the DNA methyltransferase (DNMT) inhibitor 5-aza-deoxycytidine. We hypothesized, therefore, that genes epigenetically silenced by promoter methylation are potentially key regulators of senescence. We used microarrays to compare the epigenetic gene expression profiles of precrisis LFS cells with immortal LFS cells. Gene ontology analysis of the expression data revealed a statistically significant contribution of interferon pathway, cell cycle, and cytoskeletal genes in the process of immortalization. The identification of the genes and pathways regulating immortalization will lead to a better understanding of cellular immortalization and molecular targets in cancer and aging.
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PMID:Expression profiling identifies three pathways altered in cellular immortalization: interferon, cell cycle, and cytoskeleton. 1696 18

Carcinogenic transformation of a cell requires bypassing senescence and becoming immortalized. A cellular senescence-like phenotype can be induced in immortal Li-Fraumeni syndrome (LFS) cells by treating them with the DNA methyltransferase inhibitor 5-aza-deoxycytidine. Our microarray-based expression profiling studies of spontaneously immortalized LFS cell lines identified genes that may provide the growth advantage required for the cells to become immortal. Several members of the IGFBP superfamily of genes fit the profile of genes involved in immortalization: silenced during immortalization and reactivated by 5-aza-deoxycytidine. Overexpression of IGFBP3 or IGFBPrP1 in the immortal LFS cell lines suppressed cell growth and inhibited colony formation. Both genes have the expression pattern of an epigenetically regulated gene and contain CpG islands suitable for methylation-dependent silencing. Analysis of how IGFBPs regulate immortalization will lead to a better understanding of this process and may lead to novel methods for the prevention and treatment of cancer.
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PMID:Epigenetic and functional analysis of IGFBP3 and IGFBPrP1 in cellular immortalization. 1745 53