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[Contribution of eukaryotic initiation factor-4E inhibition to heparanase expression and activity in human colon adenocarcinoma cell line LS-174T].

Objective To determine whether the eukaryotic initiation factor-4E(eIF-4E) is involved i n the cap-dependent translationa l regulation of heparanase and study the correlation between heparanase expressi on and metastatic potential of LS-174T cells. Methods The protein and mRNA levels of inhibited eIF-4E were tested by Western blot and RT-PCR. Heparanase activ ity was defined as the ability to degrade high molecular weig ht(40- 100 000 ) radiolabeled( 35 S) heparan sulfate (HS) substrate into low m olecular weight(5-15 000) HS fragments. The invasive potential of tumor cells i n vitro was observed by Matrigel invasion assay system. Results The 20-mer antisense oligonucleotide (asODN) a gainst eIF-4E specifically and significantly inhibited eIF-4E expression at bo th transcriptional and translational levels. The expression and the activ ity of heparanase were effectively lowered,which further decreased the invasive potential of LS-174T. Conclusion eIF-4E, probably being involved in translational regulation of heparanase in colon adenocarcinoma cell line LS-174T, can be a particularly interesting targe t for heparanase regulation, based on of its critical function.