title: Exogenous expression of UHRF1 promotes proliferation and metastasis             of breast cancer cells.
abstract: In the present study, we investigated the role of UHRF1 (ubiquitin-like protein containing PHD and RING finger domains 1) in proliferation, invasion and migration of breast cancer cells, and the potential mechanisms were also explored. Cell proliferation was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; cell cycle distribution and apoptosis were evaluated using flow cytometry; protein expression was determined by western blotting; angiogenesis of xenografts was assessed by microvessel density (MVD); cell invasion was measured using transwell chamber; cell migration was determined by wound scratching assay. Our results demonstrated that UHRF1 transfection conferred serum independence to MDA-MB-231 cells, G1 phase shortage and apoptosis suppression, accompanied with an increased expression of cyclin D1 and decreased expression of Bax. Significant pro-invasion and pro-migration activity was observed, with no obvious effect on the expression of PTEN and maspin. Co-expression of the UHRF1/PTEN or UHRF1/maspin degraded the role of UHRF1 in regulating invasion and migration. UHRF1 induced growth of MDA-MB-231 cells by promoting tumor vessel formation in vivo. In conclusion, UHRF1 promoted the proliferation of breast cancer cells by apoptosis inhibition, G1 phase shortage and promotion of tumor vessel formation, and pro-invasion and pro-migration activity was also observed by interacting with PTEN and maspin. Thus, UHRF1 may serve as a new therapy target for breast cancer.
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, Jiangsu, PR China. lixinli@suda.edu.cn
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Jiu-Hong
authors.initials: JH
authors.lastname: Xu
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Nie
authors.forename: Sai-Jun
authors.initials: SJ
authors.lastname: Fan
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism; D047368:Tumor Burden; D044767:Ubiquitin-Protein Ligases
chemical_list: D051017:Apoptosis Regulatory Proteins; D022762:CCAAT-Enhancer-Binding Proteins; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases