Rj. Defatta et al., Antisense RNA to eIF4E suppresses oncogenic properties of a head and neck squamous cell carcinoma cell line, LARYNGOSCOP, 110(6), 2000, pp. 928-933
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 preferentia
l upregulation of two angiogenic factors, vascular endothelial growth facto
r (VEGF) and basic fibroblast growth factor (FGF-8). We wanted to determine
whether reducing eIF4E in a HNSCC cell line could suppress its oncogenic p
roperties and in turn decrease expression of VEGF and FGF-2, Methods: Level
s of eIF4E protein expression were determined in a panel of HNSCC cell line
s. 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 transfecti
on, Western blot analysis was performed to determine the level of eIF4E and
FGF-2 reduction, while an enzyme-linked immunosorbent assay (ELISA) was us
ed to determine the level of VEGF reduction. In vitro and in vivo experimen
ts were performed to determine whether there was a reversion in the tumorig
enic properties of the FaDu cells. Results: All six cell lines had elevated
levels of eIF4E compared with Detroit 551, a normal cell line. Reducing eI
F4E expression via antisense RNA suppressed both the tumorigenic and angiog
enic properties of the FaDu cells, as demonstrated by loss of capacity to g
row in soft agar, reduced expression of angiogenic factors, and loss of tum
origenicity in nude mice. Conclusions: Antisense RNA therapy to eIF4E can p
otentially be used as adjuvant therapy for head and neck cancers, particula
rly in cases in which elevated eIF4E is found in the surgical margins.