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

Abstract:

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.

journal_name

BJU Int

journal_title

BJU international

authors

Luo Y,He DL,Ning L,Shen SL,Li L,Li X,Zhau HE,Chung LW

doi

10.1111/j.1464-410X.2006.06480.x

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

1315-9

issue

6

eissn

1464-4096

issn

1464-410X

pii

BJU6480

journal_volume

98

pub_type

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