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Mol Med Rep. 2014 Nov;10(5):2595-600. doi: 10.3892/mmr.2014.2517. Epub 2014 Aug 26.

TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion.

Author information

1
Department of Orthopedics, Central Hospital of Jingzhou, Hubei 434100, P.R. China.
2
Department of Medical Oncology, Shanghai Changzheng Hospital, Shanghai 200070, P.R. China.
3
The First Affiliated Hospital of Xin‑Xiang Medical University, Weihui, Henan 453100, P.R. China.
4
Department of Orthopedics, Orthopaedics Hospital of Nanyang, Nanyang, Henan 473003, P.R. China.
5
Shanghai Hengrui Pharmaceutical Co., Ltd, Shanghai 20035, P.R. China.
6
Shanghai Xuhai Biological Technology Co., Ltd, Shanghai 20032, P.R. China.
7
Department of Pharmaceutical Biotechnology, College of Life Sciences, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
8
Department of Surgery, Shanghai Tongren Hospital of Changning, Shanghai 200050, P.R. China.

Abstract

Histone deacetylases (HDACs) are important in chromatin remodeling and epigenetic regulation of gene expression. Histone deacetylase inhibitors (HDACi) have highly effective anti-metastatic and anti-angiogenic activity in various types of cancer, while the molecular mechanisms involved in this process are not fully understood. In the present study, trichostatin A (TSA), a HDACi, was found to suppress MCF-7 breast carcinoma cell invasion and upregulate TET1 expression in a dose-dependent manner. TET1, a dioxygenase involved in cytosine demethylation, is downregulated during breast cancer progression. TET1 knockdown in MCF-7 cells facilitates cell invasion, inhibits the expression of tissue inhibitors of metalloproteinase 2/3 (TIMP2/3) and promotes matrix metalloproteinases (MMP) 2/9 transcriptional activity. Importantly, TET1 depletion impaired the inhibitory effect of TSA on breast cancer cell invasion. Together, these results illustrated a mechanism by which TET1 partially mediates HDACi elicited suppression of breast cancer invasion.

PMID:
25175940
DOI:
10.3892/mmr.2014.2517
[Indexed for MEDLINE]

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