Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells

Kim,Young Il; Park,Seung-Won; Kwon,Hye Shin; Yang,Hyung-Seok; Cho,Sun Young; Kim,Young Jin; Lee,Hee Joo

doi:10.3892/ijo.2017.3895

Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells

Authors:
- Young Il Kim
- Seung-Won Park
- Hye Shin Kwon
- Hyung-Seok Yang
- Sun Young Cho
- Young Jin Kim
- Hee Joo Lee
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Affiliations: Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea, Department of Biotechnology, Catholic University of Daegu, Daegu 38430, Republic of Korea, Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Published online on: March 2, 2017 https://doi.org/10.3892/ijo.2017.3895
Pages: 1403-1412

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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.

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