title: Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells.
abstract: The inhibin-α gene was identified as a tumor suppressor gene in the gonads and adrenal glands by functional studies using knockout mice. Methylation of CpG sites within the regulatory regions of tumor suppressor gene is frequently associated with their transcriptional silencing. We investigated epigenetic modifications, changes in loss of heterozygosity (LOH), and mutation of the inhibin-α gene, and regulation of transcriptional expression in response to inhibitors of DNA methylation (5-aza-2'-deoxycytidine, 5-AzaC) in human lymphoid (Jurkat, Molt-4, Raji, and IM-9) and myeloid (HL-60, Kasumi-1, and K562) leukemia cells. The inhibin-α promoter was hypermethylated in lymphoid (Molt-4 and Raji) and myeloid (HL-60 and Kasumi-1) leukemia cells. Inhibin-α gene mutations differed significantly between lymphoid (heterozygote) and myeloid (homozygote) leukemia cells. LOH in the inhibin-α gene was detected in lymphoid and myeloid leukemia cells, with the exception of Jurkat cells. Treatment with 5-AzaC, a demethylating agent, resulted in increased inhibin-α mRNA and protein levels in most of the cell lines. Also, 5-AzaC treatment inhibited cell proliferation and induced apoptosis. Taken together, our results reveal that the inhibin-α gene is transcriptionally silenced in human leukemia cells and that reactivation is suppressed by a demethylating agent. In addition, mutations in, and expression levels of, the inhibin-α gene differed between human lymphoid and myeloid leukemia cells.
authors.affiliation: Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Catholic University of Daegu, Daegu 38430, Republic of Korea.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Hye Shin
authors.initials: HS
authors.lastname: Kwon
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Hee Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007265:Inhibins / Q000235:genetics*; D007945:Leukemia, Lymphoid / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C094377:inhibin-alpha subunit; D007265:Inhibins; D000077209:Decitabine; D001374:Azacitidine