title: Wnt-β-catenin-Tcf-4 signalling-modulated invasiveness is dependent on osteopontin expression in breast cancer.
abstract: BACKGROUND
  We have previously demonstrated that Tcf-4 regulates osteopontin (OPN) in rat breast epithelial cells, Rama37. In this report, we have examined the importance of this regulation in human breast cancer.
  
  
  METHODS
  The regulatory roles of Tcf-4 on cell invasion and OPN expression were investigated. The mRNA expression of Tcf-4 and OPN, and survival of breast cancer patients were correlated.
  
  
  RESULTS
  Tcf-4 enhanced cell invasion in both MCF10AT and MDA MB 231 breast cancer cells by transcriptionally activating OPN expression. Osteopontin was activated by Wnt signalling in MDA MB 231 cells. Paradoxical results on Tcf-4-regulated OPN expression in MCF10AT (activation) and Rama37 (repression) cells were shown to be a result of differential Wnt signalling competency in MCF10AT and Rama37 cells. High levels of OPN and Tcf-4 mRNA expression were significantly associated with survival in breast cancer patients. Most importantly, Tcf-4-positive patients had a poorer prognosis when OPN was overexpressed, while OPN-negative patients had a better prognosis when Tcf-4 was overexpressed.
  
  
  CONCLUSIONS
  Our results suggest that Tcf-4 can act as a repressor or activator of breast cancer progression by regulating OPN expression in a Wnt-dependent manner and that Tcf-4 and OPN together may be a novel prognostic indicator for breast cancer progression.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ravindranath
authors.forename: H-F
authors.initials: HF
authors.lastname: Yuen
authors.forename: K-K
authors.initials: KK
authors.lastname: Chan
authors.forename: C
authors.initials: C
authors.lastname: Grills
authors.forename: D A
authors.initials: DA
authors.lastname: Fennell
authors.forename: T R
authors.initials: TR
authors.lastname: Lappin
authors.forename: M
authors.initials: M
authors.lastname: El-Tanani
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D047369:Chromatin Immunoprecipitation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D053495:Osteopontin / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D040081:Protein Array Analysis; D015398:Signal Transduction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D053495:Osteopontin