title: Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells.
abstract: BACKGROUND
  Bcl-2 (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis. Although much is known about the anti-apoptotic ability of Bcl-2, little information is available concerning its function in other cellular processes, such as cell differentiation.
  
  
  METHODS
  In this study, stable cell lines from pre-malignant MCF10ATG3B mammary epithelial cells, a cell line derived from a human proliferative breast disease model, to express exogenous Bcl-2 was established. CMV promoter driven Bcl-2 expression vector or empty vector was transfected into MCF10ATG3B human mammary epithelial cells to investigate the effects of Bcl-2 on mammary epithelial cells. In addition, western blot and immunofluoresence staining were employed to testify the marker proteins of both mesenchymal and epithelial cells.
  
  
  RESULTS
  Unexpectedly, a dramatic change of phenotype from epithelial cells to fibroblast-like cells was observed in Bcl-2-transfected cells. Western blot analysis and immunofluoresence staining results demonstrated that the E-cadherin and desmoplakin, markers of epithelial cells, were downregulated in the Bcl-2-transfected cells. However, N-cadherin and vimentin, markers of mesenchymal cells, were upregulated in these cells. Redistributions of cytokeratin and beta-catenin were also observed in the Bcl-2-transfected cells. Our results further showed that the Bcl-2-transfected MCF10ATG3B cells retained some epithelial markers, such as epithelial specific antigen (ESA) and epithelial membrane antigen (EMA), indicating their epithelial origin. In addition, cell migration and invasion was substantially increased in Bcl-2 transfected cells.
  
  
  CONCLUSIONS
  Taken together, our results strongly indicate that in addition to its anti-apoptotic function, Bcl-2 is also involved in the epithelial-mesenchymal transition (EMT), a fundamental mechanism in normal morphogenesis and pathogenesis of some diseases.
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. angel0311@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: An
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. lvjin6630@hotmail.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Lv
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. liaimin53@sina.com.|Department of Hepatobiliary Surgery, The Second Artillery General Hospital, Beijing, 100088, China. liaimin53@sina.com.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. qjxiao@126.com.
authors.forename: Junxiao
authors.initials: J
authors.lastname: Qiao
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. 49452525@qq.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. 39456001@qq.com.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. Linghberg@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. zhao.wei@stu.xjtu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. Chenhuoming1881@sina.com.
authors.forename: Huoming
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Second Artillery General Hospital, PLA, Beijing, 100088, China. drwangliying@live.cn.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D014746:Vimentin