title: Role of insulin-like growth factor binding protein-4 in prevention of colon cancer.
abstract: BACKGROUND
  Insulin-like growth factors (IGFs) are important for the proliferation of cancer cells. One of their binding proteins, known as insulin-like growth factor binding protein -4 (IGFBP-4) is well known for its inhibitory action on IGFs in vitro. We assessed the effect of IGFBP-4 in prevention of development of colon cancer in vivo.
  
  
  METHODS
  Nude mice were subcutaneously inoculated with HT-29 colon cancer cells and they were also simultaneously injected either gene construct containing mammalian expression vector pcDNA3 with or without IGFBP-4 gene or phosphate buffered saline. The effect was assessed 4 weeks later by evaluating the tumours for mitosis, necrosis, apoptosis, and expressions of IGFBP-4, Bcl-2 and Bax proteins.
  
  
  RESULTS
  The results showed that the IGFBP-4 gene therapy did not prevent the tumour establishment but it increased the tumour apoptosis which was associated with an increase in Bcl-2 and Bax expressions. The IGFBP-4 protein was low in tumours which received IGFBP-4 gene construct which may be due to a feed back mechanism of IGFBP-4 upon its own cells.
  
  
  CONCLUSIONS
  IGFBP-4 gene therapy in the form localised gene transfer did not prevent colon cancer initiation and establishment but it resulted in increased apoptosis and Bax protein expression and a decrease in tumour cellular mitosis.
authors.affiliation: Academic Division of Surgical and Interventional Sciences, University College London, London, UK. a.seifalian@ucl.ac.uk.
authors.forename: Rajaraman
authors.initials: R
authors.lastname: Durai
authors.forename: Shi Y
authors.initials: SY
authors.lastname: Yang
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Goldspink
authors.forename: Marc C
authors.initials: MC
authors.lastname: Winslet