title: Reduced expression of BMPR-IB correlates with poor prognosis and increased proliferation of breast cancer cells.
abstract: BACKGROUND
  Breast cancer is the leading female cancer in the UK. Recent work has shown that Bone Morphogenetic Proteins (BMPs) and their receptors may be involved in the progression of breast cancer. The aim of the current study is to identify the role of BMPR-IB, one of these receptors, in breast cancer.
  
  
  METHODS
  Expression of BMPR-IB was examined in a cohort of breast tissue samples. The transcript level was determined using quantitative real time-PCR and protein levels were assessed with immunohistochemical staining (IHC). Constructed ribozyme transgenes were used to knock-down BMPR-IB in MDA-MB-231 cells, and the effect this had on in vitro cell growth was examined.
  
  
  RESULTS
  Decreased staining of BMPR-IB was seen in most of the breast tumour samples examined compared to normal breast tissues. Q-PCR analysis revealed lower expression levels of BMPR-IB transcript in patient samples with a predicted poor prognosis (Nottingham prognosis index (NPI) >5.4) (8.2+/-17, p=0.03) compared to samples with a good prognosis (NPI <3.4) (469+/-244). Higher BMPR-IB expression was seen in samples from disease free patients compared to those with poorer prognosis; including patients with metastasis, local recurrence and breast cancer deaths, (p=0.026). Furthermore, down-regulation of BMPR-IB in MDA-MB-231cells led to a promotion of in vitro cell growth.
  
  
  CONCLUSIONS
  This study shows that decreased expression of BMPR-IB correlates with poor prognosis in breast cancer patients and leads to increased cell proliferation of breast cancer cells in vitro. This suggests that BMPR-IB mediates an inhibitory effect on breast cancer cells.
authors.affiliation: Metastasis and Angiogenesis Research Group, Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK. bokobzasm@cf.ac.uk
authors.forename: Sivan M
authors.initials: SM
authors.lastname: Bokobza
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Howard E
authors.initials: HE
authors.lastname: Kynaston
authors.forename: Robert E
authors.initials: RE
authors.lastname: Mansel
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I