title: Silencing of the annexin II gene down-regulates the levels of S100A10, c-Myc, and plasmin and inhibits breast cancer cell proliferation and invasion.
abstract: OBJECTIVE
  To explore the roles of annexin II in breast cancer progression, and to study the effect of annexin II on breast cancer cell proliferation and invasion.
  
  
  METHODS
  This study was conducted in the Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China from December 2006 to January 2009. First, we employed Western blot and reverse transcriptase polymerase chain reaction to detect the expression of annexin II and S100A10 in a panel of well-characterized human breast cancer cell lines, and investigated the localization of annexin II and S100A10 by use of immunofluorescence. We then silenced the expression of annexin II in MDA-MB-435s, which was found to over express annexin II, using the chemically-synthetic annexin II small interfering RNA (siRNA) duplexes (including 3 groups: blank MDA-MB-435s cells, cells transfected with negative control siRNA, and cells transfected with annexin II-siRNA). Finally, the cell proliferation, invasion, and plasmin generation were assayed, and the cellular levels of S100A10 and c-Myc were also detected. All the tests were repeated 3 times.
  
  
  RESULTS
  Annexin II and S100A10 were over expressed in invasive human breast cancer cell lines. The siRNA targeting annexin II of MDA-MB-435s cells did not only decrease annexin II messenger RNA and protein levels, but also down-regulated the levels of S100A10, and c-Myc. The treated cells were remarkably blocked in the G0/G1 phase, and cells in the S/G2+M phase decreased. Additionally, the treatment with siRNA resulted in reduction of plasmin generation as well as a loss of the invasive capacity of breast cancer cells.
  
  
  CONCLUSIONS
  Annexin II might be a key contributor to breast cancer proliferation and invasion.
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Bianqin
authors.initials: B
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.forename: Tingmei
authors.initials: T
authors.lastname: Chen
mesh_terms: D017306:Annexin A2 / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D005341:Fibrinolysin; D020598:Proto-Oncogene Proteins c-myb; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10