Nuclear-encoded mitochondrial MTO1 and MRPL41 are regulated in an opposite epigenetic mode based on estrogen receptor status in breast cancer

BMC Cancer

Tae Woo Kim²  Byungtak Kim²  Ju Hee Kim²  Seongeun Kang²  Sung-Bin Park²  Gookjoo Jeong²  Han-Sung Kang¹  Sun Jung Kim² 

[1] Research Institute and Hospital, National Cancer Center, Gyeonggi do 411-764, Korea

[2] Department of Life Science, Dongguk University-Seoul, Seoul 100-715, Korea

关键词: MTO1;    MRPL41;    Estrogen receptor;    Epigenetics;    Breast cancer;   

Others  :  1079492
DOI  :  10.1186/1471-2407-13-502

 received in 2013-06-28, accepted in 2013-10-22,  发布年份 2013

【 摘 要 】

Background

MTO1 and MRPL41 are nuclear-encoded mitochondrial genes encoding a mitochondrial tRNA-modifying enzyme and a mitochondrial ribosomal protein, respectively. Although both genes have been known to have potential roles in cancer, little is known about their molecular regulatory mechanism, particularly from an epigenetic approach. In this study, we aimed to address their epigenetic regulation through the estrogen receptor (ER) in breast cancer.

Methods

Digital differential display (DDD) was conducted to identify mammary gland-specific gene candidates including MTO1 and MRPL41. Promoter CpG methylation and expression in breast cancer cell lines and tissues were examined by methylation-specific PCR and real time RT-PCR. Effect of estradiol (E2), tamoxifen, and trichostatin A (TSA) on gene expression was examined in ER + and ER- breast cancer cell lines. Chromatin immunoprecipitation and luciferase reporter assay were performed to identify binding and influencing of the ER to the promoters.

Results

Examination of both cancer tissues and cell lines revealed that the two genes showed an opposite expression pattern according to ER status; higher expression of MTO1 and MRPL41 in ER- and ER+ cancer types, respectively, and their expression levels were inversely correlated with promoter methylation. Tamoxifen, E2, and TSA upregulated MTO1 expression only in ER+ cells with no significant changes in ER- cells. However, these chemicals upregulated MRPL41 expression only in ER- cells without significant changes in ER+ cells, except for tamoxifen that induced downregulation. Chromatin immunoprecipitation and luciferase reporter assay identified binding and influencing of the ER to the promoters and the binding profiles were differentially regulated in ER+ and ER- cells.

Conclusions

These results indicate that different epigenetic status including promoter methylation and different responses through the ER are involved in the differential expression of MTO1 and MRPL41 in breast cancer.

【 授权许可】

   
2013 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

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