Antisense RNA to eIF4E suppresses oncogenic properties of a head and neck squamous cell carcinoma cell line.
OBJECTIVE
The translation initiation factor eIF4E is elevated in all head and neck squamous cell cancers (HNSCCs) and appears to be essential in the progression of solid tumors. Overexpression of eIF4E results in preferential upregulation of two angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). We wanted to determine whether reducing eIF4E in a HNSCC cell line could suppress its oncogenic properties and in turn decrease expression of VEGF and FGF-2.


METHODS
Levels of eIF4E protein expression were determined in a panel of HNSCC cell lines. An episomal vector containing antisense RNA to eIF4E was used to reduce the eIF4E level in one of these cell lines, FaDu. After a stable transfection, Western blot analysis was performed to determine the level of eIF4E and FGF-2 reduction, while an enzyme-linked immunosorbent assay (ELISA) was used to determine the level of VEGF reduction. In vitro and in vivo experiments were performed to determine whether there was a reversion in the tumorigenic properties of the FaDu cells.


RESULTS
All six cell lines had elevated levels of eIF4E compared with Detroit 551, a normal cell line. Reducing eIF4E expression via antisense RNA suppressed both the tumorigenic and angiogenic properties of the FaDu cells, as demonstrated by loss of capacity to grow in soft agar, reduced expression of angiogenic factors, and loss of tumorigenicity in nude mice.


CONCLUSIONS
Antisense RNA therapy to eIF4E can potentially be used as adjuvant therapy for head and neck cancers, particularly in cases in which elevated eIF4E is found in the surgical margins.
DeFatta
R J
RJ
Department of Biochemistry, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Nathan
C A
CO
De Benedetti
A
A
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D039561:Eukaryotic Initiation Factor-4E; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D010448:Peptide Initiation Factors / Q000187:drug effects*; D016372:RNA, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D039561:Eukaryotic Initiation Factor-4E; D008222:Lymphokines; D010448:Peptide Initiation Factors; D016372:RNA, Antisense; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2