Over-expression of hypoxia-inducible factor-1alpha increases the invasive potency of LNCaP cells in vitro

BJU Int. 2006 Dec;98(6):1315-9. doi: 10.1111/j.1464-410X.2006.06480.x. Epub 2006 Sep 6.


Objective: To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha) over-expression on the invasion-associated proteins in human prostate cancer cells, as HIF-1alpha is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance the invasive potency of prostate cancer cells.

Materials and methods: Prostate cancer (LNCaP) cells were transfected with recombinant plasmid pcDNA3.1(-)/HIF-1alpha and pcDNA3.1(-) control vector using a commercial system, designated as LNCaP/HIF-1alpha and LNCaP/pcDNA3.1, respectively. The positive clones were selected with G418 and confirmed by Western blot and indirect immunofluorescence labelling. A polycarbonate filter, coated with a matrix gel, was used to analyse the invasive potency. The expression of E-cadherin, vimentin, cathepsin D, matrix metalloproteinase (MMP2) and urokinase plasminogen activator receptor (uPAR) was detected by Western blot.

Results: The expression level of HIF-1alpha in LNCaP/HIF-1alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. Many more cells of LNCaP/HIF-1alpha penetrated through the polycarbonate filter than those of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin, cathepsin D, MMP-2 and uPAR were up-regulated in LNCaP/HIF-1alpha, whereas the expression of E-cadherin was down-regulated.

Conclusion: These results show that over-expression of HIF-1alpha directly stimulates the invasive potency of human prostate carcinoma LNCaP cells through the matrix gel. The expression of E-cadherin, vimentin, cathepsin D, MMP-2 and uPAR, which are proteins with established roles in the pathophysiology of invasion, could be regulated by HIF-1alpha in human prostate cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • Neoplasm Invasiveness / pathology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Transfection
  • Tumor Cells, Cultured


  • Hypoxia-Inducible Factor 1, alpha Subunit