Role Of DNA Methyltransferase 1, “DNMT 1” In Human Cancer

Abstract

Changes in methylation of promoter or first exon may mimic the effect of mutations of various tumor suppressor genes (TSGs) or proto- oncogene. Repression of various genes during malignant transformation is due to CpG island hypermethylation and chromatin remodeling. Transcriptional-silencing is due to the Hypermethylation of promoter of various TSGs. However, hypomethylation of regulatory DNA sequences activates transcription of proto-oncogene, retrotransposons, as well as genes encoding proteins involved in genomic instability and malignant cell metastasis. The methylation of genomic DNA in malignant cells is catalyzed by DNA methyltransferases DNMT1. DNA methylation can be induced by the tobacco-specific carcinogen NNK. The role of DNMT1-mediated methylation in tobacco carcinogenesis remains unclear. In a human lung cell line, glycogen synthase kinase 3β (GSK3β) phosphorylatedDNMT1 to recruit β-transducin repeat–containing protein (βTrCP), resulting in DNMT1 degradation, and that NNK activated AKT, inhibiting GSK3β function and thereby attenuating DNMT1 degradation. Chemotherapy using DNA intercalators is one of the most successful approaches to cancer treatment. Induction of apoptosis in tumor cells is due t DNA intercalators that are believed to inhibit DNA polymerases and topo-isomerases, . The inhibition of DNMT1 the primary DNA methyltransferase in mammalian cells ,enzymatic activity is done by the DNA intercalators, such as doxorubicin. Expression levels of DNMT1 in tumor cells may affect the effectiveness of doxorubicin in chemotherapy. Global hypomethylation in the absence of DNMT1down-regulation is apparent in non-primate placentas and invitro derived human cyto-trophoblast stem cells, suggesting that DNMT1down-regulation is not an absolute requirement for genomic hypomethylation in all instances. Here, we worked with the lymph node cancer tissue and found that the suppression of the activity along with other effects caused by other genes is responsible for the cancer development in the lymph node tissue.