title: Down-regulation of nicotinamide N-methyltransferase induces apoptosis in human breast cancer cells via the mitochondria-mediated pathway.
abstract: Nicotinamide N-methyltransferase (NNMT) has been found involved in cell proliferation of several malignancies. However, the functional role of NNMT in breast cancer has not been elucidated. In the present study, we showed that NNMT was selectively expressed in some breast cancer cell lines, down-regulation of NNMT expression in Bcap-37 and MDA-MB-231 cell lines by NNMT shRNA significantly inhibited cell growth in vitro, decreased tumorigenicity in mice and induced apoptosis. The silencing reciprocal effect of NNMT was confirmed by over-expressing NNMT in the MCF-7 and SK-BR-3 breast cancer cell lines which lack constitutive expression of NNMT. In addition, down-regulation of NNMT expression resulted in reducing expression of Bcl-2 and Bcl-xL, up-regulation of Bax, Puma, cleaved caspase-9, cleaved caspase-3 and cleaved PARP, increasing reactive oxygen species production and release of cytochrome c from mitochondria, and decreasing the phosphorylation of Akt and ERK1/2. These data suggest that down-regulation of NNMT induces apoptosis via the mitochondria-mediated pathway in breast cancer cells.
authors.affiliation: Clinical Laboratory, Sir RunRun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Sir RunRun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Sir RunRun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical Laboratory, Sir RunRun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Clinical Laboratory, Sir RunRun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China ; Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Xinyou
authors.initials: X
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D050903:Nicotinamide N-Methyltransferase / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D045304:Cytochromes c; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase; C022616:thiazolyl blue