LATS2 promoter hypermethylation and its effect on gene expression in human breast cancer

Matsui,Saki; Kagara,Naofumi; Mishima,Chieko; Naoi,Yasuto; Shimoda,Masafumi; Shimomura,Atsushi; Shimazu,Kenzo; Kim,Seung  Jin; Noguchi,Shinzaburo

doi:10.3892/ol.2017.7535

February-2018 Volume 15 Issue 2

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February-2018 Volume 15 Issue 2

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Article

LATS2 promoter hypermethylation and its effect on gene expression in human breast cancer

Authors:
- Saki Matsui
- Naofumi Kagara
- Chieko Mishima
- Yasuto Naoi
- Masafumi Shimoda
- Atsushi Shimomura
- Kenzo Shimazu
- Seung Jin Kim
- Shinzaburo Noguchi
View Affiliations / Copyright

Affiliations: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan
Pages: 2595-2603
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Published online on: December 6, 2017

https://doi.org/10.3892/ol.2017.7535
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Abstract

Tumor‑specific promoter hypermethylation of large tumor suppressor, homolog 2 (LATS2), a tumor suppressor gene, has been investigated using methylation‑specific polymerase chain reaction (MSP) assays in different types of human cancer producing conflicting results. The aim of the present study was to evaluate the methylation status of the LATS2 promoter region using bisulfite sequencing with a next generation sequencer for breast cancer. In the 11 patients enrolled in the present study, the LATS2 promoter methylation index (MI) was uniformly high in tumor and normal tissues of the breast (median, 84.0 and 87.4%, respectively). The presence of LATS2 promoter hypermethylation was confirmed in isolated tumor cells and normal epithelial cells using the magnetic‑activated cell sorting method. In situ hybridization for LATS2 messenger RNA (mRNA) revealed that the mRNA expression of LATS2 was higher in normal epithelial cells, compared with tumor cells, however, it was not significantly associated with LATS2 MI. In 12 breast cancer cell (BCC) lines and two normal breast cell lines, the LATS2 promoter was uniformly hypermethylated with no correlation between the mRNA expression of LATS2 and the LATS2 MI. In addition, treatment of the BCC lines with a demethylating reagent had minimal effect on the mRNA expression of LATS2 in any of these cell lines. These results demonstrated that LATS2 hypermethylation was not involved in silencing the mRNA expression of LATS2 mRNA. The lower mRNA expression level of LATS2 in tumor cells, compared with normal epithelial cells, suggested the possible involvement of downregulation in the mRNA expression of LATS2 in the pathogenesis of breast cancer. Therefore, the conflicting results previously reported for LATS2 promoter methylation in different types of cancer, detected using MSP assays may be attributable to the low fidelity of the MSP assay.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

LATS2 promoter hypermethylation and its effect on gene expression in human breast cancer

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