title: MiR-221/-222 differentiate prognostic groups in advanced breast cancers and influence cell invasion.
abstract: BACKGROUND
  MiR-221/-222 are frequently overexpressed in breast cancer and are associated with increased malignancy. The specific modification of microRNAs (miRNAs) expression could be a promising strategy in breast cancer therapy, leading to the suppression of tumourigenic processes in tumour cells.
  
  
  METHODS
  MiR-221/-222 expressions were analysed in 86 breast cancer tissues by quantitative RT-PCR and tested for correlation with immunohistochemistry data and clinical follow-up. In vitro assays were conducted using human breast cancer cell lines with lentiviral overexpression of miR-221/-222.
  
  
  RESULTS
  In tumour tissues, miR-221/-222 were associated with the occurrence of distant metastases. In particular, high levels of miR-221 were revealed to have a high prognostic impact for the identification of significantly different groups with advanced tumours. MiR-221/-222 overexpression strongly increased cell proliferation and invasion in vitro. Following miR-221/-222 overexpression an increased uPAR expression and cell invasion were observed.
  
  
  CONCLUSIONS
  This study demonstrates a significant role for highly expressed miR-221/-222 in advanced breast cancers allowing for the identification of significantly different prognostic groups, particularly for HER2-positive and lymph-node-positive breast cancers. Considering that miR-221/-222 are strongly involved in cell invasion, these miRNAs may be promising markers for breast cancer prognosis and therapy.
authors.affiliation: Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Falkenberg
authors.forename: N
authors.initials: N
authors.lastname: Anastasov
authors.forename: K
authors.initials: K
authors.lastname: Rappl
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: G
authors.initials: G
authors.lastname: Auer
authors.forename: A
authors.initials: A
authors.lastname: Walch
authors.forename: M
authors.initials: M
authors.lastname: Huber
authors.forename: I
authors.initials: I
authors.lastname: Höfig
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
authors.forename: H
authors.initials: H
authors.lastname: Höfler
authors.forename: M J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: M
authors.initials: M
authors.lastname: Aubele
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C525709:MIR221, human; C525710:MIR222, human