[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 in the cap-dependent translational regulation of heparanase and study the correlation between heparanase expression 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 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.


RESULTS
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.


CONCLUSIONS
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.
Yang
Yu-jie
YJ
Institute of Digestive Diseases, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
Zhang
Ya-li
YL
Lai
Zhuo-sheng
ZS
Wang
Ji-de
JD
Wu
Bao-ping
BP
Wang
Ya-dong
YD
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D000099175:Heparanase
D039561:Eukaryotic Initiation Factor-4E; D005966:Glucuronidase; D000099175:Heparanase