Research Papers:

Suberoylanilide hydroxamic acid-induced specific epigenetic regulation controls Leptin-induced proliferation of breast cancer cell lines

Xiuyan Feng, Han Han, Dan Zou, Jiaming Zhou and Weiqiang Zhou _

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Oncotarget. 2017; 8:3364-3379. https://doi.org/10.18632/oncotarget.13764

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Xiuyan Feng1,2, Han Han2, Dan Zou2, Jiaming Zhou3, Weiqiang Zhou2

1The Second Affiliated Hospital of Shenyang Medical College, Heping District, Shenyang City, Liaoning Province 110002, P. R. China

2Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, Huanggu District, Shenyang City, Liaoning Province 110034, P. R. China

3Northeast Yucai Foreign Language School, Hunnan New District, Shenyang City, Liaoning Province 110179, P. R. China

Correspondence to:

Weiqiang Zhou, email: [email protected]

Keywords: suberoylanilide hydroxamic acid, histone acetylation, breast cancer

Received: July 28, 2016     Accepted: November 22, 2016     Published: December 01, 2016


Breast cancer is one of the most common malignancies among women in the world, investigating the characteristics and special transduction pathways is important for better understanding breast development and tumorigenesis. Leptin, a peptide hormone secreted from white adipocytes, may be an independent risk factor for breast cancer.

Here, we treated suberoylanilide hydroxamic acid (SAHA) on Leptin-induced cell proliferation and invasion in the estrogen-receptor-positive breast cancer cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. Low concentrations of Leptin (0.625 nM) significantly stimulated breast cancer cell growth, enhanced cell viability, minimized apoptosis, and increased cell cycle transition. In contrast, SAHA (5 μM) treatment had reverse effects. Wound healing assay showed that, in MCF-7 and MDA-MB-231 cell line, cell migrating stimulated by Leptin was significantly repressed with SAHA treatment. Moreover, cell cycle real-time PCR array and proteome profiler antibody array confirmed that Leptin and SAHA treatment significantly changed the expressions of factors associated with cell cycle regulation and apoptosis including p53 and p21WAF1/CIP1.

In DNA-ChIP analysis, we found that acetylation levels binding with p21WAF1/CIP1 promoters are regulated in a manner specific to histone type, lysine residue and selective promoter regions. SAHA significantly up-regulated the acetylation levels of AcH3-k14 and AcH3-k27 in MCF-7 cells, whereas Leptin repressed the modification. In addition, SAHA or Leptin had no significant effects on the AcH4 acetylation binding with any regions of p21WAF1/CIP1 promoter. In MDA-MB-231 cells, SAHA alone or in combination with Leptin significantly increased acetylation levels of Ach3-k27, Ach3-k18 and Ach4-k5 residues. However, no clear change was found with Leptin alone at all. Overall, our data will inform future studies to elucidate the mechanisms of p21WAF1/CIP1 transcriptional regulation, and the functional roles of p21WAF1/CIP1 in breast cancer tumorigenesis.

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