title: Suberoylanilide hydroxamic acid-induced specific epigenetic regulation controls Leptin-induced proliferation of breast cancer cell lines.
abstract: 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.
authors.affiliation: The Second Affiliated Hospital of Shenyang Medical College, Heping District, Shenyang City, Liaoning Province 110002, P. R. China.|Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, Huanggu District, Shenyang City, Liaoning Province 110034, P. R. China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, Huanggu District, Shenyang City, Liaoning Province 110034, P. R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Han
authors.affiliation: Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, Huanggu District, Shenyang City, Liaoning Province 110034, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zou
authors.affiliation: Northeast Yucai Foreign Language School, Hunnan New District, Shenyang City, Liaoning Province 110179, P. R. China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, Huanggu District, Shenyang City, Liaoning Province 110034, P. R. China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D020738:Leptin; D000077337:Vorinostat
keywords: breast cancer; histone acetylation; suberoylanilide hydroxamic acid