Seminars and Symposia
IDAC Seminar, 18 November 2011
|Secretariat, Alumni Association, IDAC|
|Date||Friday, 18 November 2011, 14:00～|
|Room||Seminar-shitsu 1,2, IDAC Research Bldg.|
|Title||BRCA1 and Global DNA Methylation,|
|Speaker||Prof. Toru Ouchi|
|Affiliation||Department of Cancer Genetics,Roswell Park Cancer Institute, Buffalo, NY|
|Person-in-charge||Natsuko Chiba Department of Molecular Immunology (ex 8478)|
|Abstract||Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. There are approximately 30,000 CpG islands in the genome and 50-60% of these are found within the promoter region of genes. The abnormal methylation causes transcriptional repression of numerous genes, leading to tumor growth and development.
Our group has recently discovered that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1. In mammary tumors developed in conditional BRCA1 knockout mice, levels of DNMT1 are significantly decreased, and subsequently global DNA methylation is also reduced. Several protooncogenes, such as c-myc, c-fos and Ha-ras, are induced in those tumors, suggesting that altered gene expression due to hypomethylation of genomic DNA contributes to carcinogenesis caused by BRCA1 deficiency. On-going projects include identification of the genes whose increased or decreased expression is correlated with promoter methylation identified above.