Contribution of eukaryotic initiation factor-4E inhibition to heparanase expression and activity in human colon adenocarcinoma cell line LS-174T / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To determine whether the eukaryotic initiation factor-4E (eIF-4E) is involved in the cap-dependent translational regulation of heparanase and study the correlation between heparanase expression and metastatic potential of LS-174T cells.</p><p><b>METHODS</b>The protein and mRNA levels of inhibited eIF-4E were tested by Western blot and RT-PCR. Heparanase activity was defined as the ability to degrade high molecular weight (40-100 000) radiolabeled ((35)S) heparan sulfate (HS) substrate into low molecular weight (5-15 000) HS fragments. The invasive potential of tumor cells in vitro was observed by Matrigel invasion assay system.</p><p><b>RESULTS</b>The 20-mer antisense oligonucleotide (asODN) against eIF-4E specifically and significantly inhibited eIF-4E expression at both transcriptional and translational levels. The expression and the activity of heparanase were effectively lowered, which further decreased the invasive potential of LS-174T.</p><p><b>CONCLUSION</b>eIF-4E, probably being involved in translational regulation of heparanase in colon adenocarcinoma cell line LS-174T, can be a particularly interesting target for heparanase regulation, based on of its critical function.</p>