title: Capillary morphogenesis gene 2 inhibits growth of breast cancer cells and is inversely correlated with the disease progression and prognosis.
abstract: BACKGROUND
  Capillary morphogenesis gene 2 (CMG2) also known as anthrax toxin receptor 2 was identified as a gene being up-regulated in capillary morphogenesis. It has been shown to be involved in cell adhesion and motility which are critical functions for cancerous cells to disseminate. The present study aimed to examine the expression of CMG2 in breast cancer and its implication in the disease progression.
  
  
  METHODS
  Breast primary tumours and background tissues were collected immediately after surgery and stored at -80 °C with approval by the local ethics committee, and written consent obtained from patients. The expression of CMG2 in 127 breast cancer tumour samples and 34 normal mammary tissues was determined using real-time PCR. Knockdown and over-expression in breast cancer cells were established using constructed plasmid vectors carrying either anti-CMG2 ribozyme or full-coding sequence of human CMG2. The effect on growth of breast cancer cells was examined using in vitro and in vivo models.
  
  
  RESULTS
  The CMG2 transcript levels were reduced in advanced tumours compared with its expression in tumours of early stage according to their TNM staging. The reduced expression was associated with shorter overall survival, p = 0.004 compared with patients who had higher expression. The knockdown of CMG2 resulted in an increased in vitro growth of MDA-MB-231 cells which express this gene at relatively higher levels. This is consistent with the finding from MCF-7 cells which express lower levels of CMG2 and exhibited reduced growth following over-expression of CMG2. The over-expression of CMG2 also demonstrated an inhibitory effect on in vivo growth of MCF-7 cells.
  
  
  CONCLUSIONS
  Reduced expression of CMG2 is associated with disease progression and poor prognosis of breast cancer. CMG2 has an inhibitory effect on growth of breast cancer cells. Further investigation is required to shed light on the prognostic and therapeutic potential of targeting this molecule.
authors.affiliation: Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, GF46, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK, yel@cf.ac.uk.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Sun
authors.forename: Muhammad Faraz Arshad
authors.initials: MF
authors.lastname: Malik
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018276:Carcinoma, Medullary / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C447150:ANTXR2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018000:Receptors, Peptide