Histone Deacetylase (HDAC) 활성 저해제에 의한 혈관신생 관련유전자 발현의 억제 작용
The Effect of Histone Deacetylase (HDAC) Inhibitors on th Expression of Angiogenesis-related Genes
김세희, 배명호, 정주원, 배문경, 권호정, 유미애, 김규원,
소속 상세정보
김세희 ( Kim Se-Hee )
부산대학교 분자생물학과
배명호 ( Bae Myung-Ho )
부산대학교 분자생물학과
정주원 ( Jung Joo-Won )
부산대학교 분자생물학과
배문경 ( Bae Moon-Kyoung )
부산대학교 분자생물학과
권호정 ( Kwon Ho-Jeong )
세종대학교 생명공학과
유미애 ( Yoo Mi-Ae )
부산대학교 분자생물학과
김규원 ( Kim Kyu-Won )
서울대학교 약학대학
KMID : 0603520010060040232
Abstract
The acetylation and deacetylation of histones play significant roles in the regulation of transcription. Histone deacetylases (HDACs) are important enzymes that regulate gene transcription and alter chromatin assembly with essential and conserved functions. Function of HDACs has been focused on their transcriptional corepression of a large number of targets in chromatin remodeling processes inside nucleus. Our previous study has suggested that HDACs regulate the expression of angiogenesis-related genes. Therefore HDACs inhibitors have a potential as anti-cancer drugs, but the detailed function on their anti-angiogenic activity is not well understood. To determine the function of HDAC inhibitors in the angiogenic process, we investigated the effect of the HDAC specific inhibitors, such as trichostatin A (TSA) and FR901228, on the expression of angiogenesis-related genes, transcription factors and a tumor suppressor gene. We performed the Western blot analysis after the treatment of HepG2 human hepatoblastoma cells with TSA of FR901228. The protein levels of angiogenesis-related genes, i.e.,VEGF, MT1-MMP, Sp1,c-Jun and c-Fos and transcription factors, i.e., Egr-1 and Ets1 were decreased by TSA and FR901228. Especially FR901228 showed a stronger inhibitory activity than TSA. The protein expression of a tumor suppressor gene, i.e., gelsolin was increased by TSA and FR901228.These results suggest that HDAC inhibitors suppress the angiogenic processes through regulation of the expression of angiogenesis-related genes.
키워드
Trichostatin A; FR901228; Histone Deacetylase inhibitor; Angiogenesis
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