Decreased proliferation of human melanoma cell lines caused by antisense RNA against translation factor eIF-4AI.

Autor: Eberle, J., Fecker, L.F., Bittner, J.-U., Orfanos, C.E., Geilen, C.C.
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Zdroj: British Journal of Cancer; 6/17/2002, Vol. 86 Issue 12, p1957, 6p
Abstrakt: Control of translation initiation was recognised as a critical checkpoint for cell proliferation and tumorigenesis. In human melanoma cells, we have previously reported consistent overexpression of translation initiation factor elF-4AI. Here, we investigated by transfection of antisense constructs its significance for the control of melanoma cell growth. The tetracyclineinducible expression system was established in melanoma cells, and three fragments of the 5'-, central-, and 3'-portion of the elF-4AI cDNA were subcloned in antisense and in sense orientation after a tetracycline inducible promoter. Significant proliferation decrease was obtained after transient transfection and induction of antisense RNA directed against the 5'- and the central portion (up to 10%), whereas, no effects were seen after induction of the 3'-fragment and the sense controls. Cell clones stably transfected with the central antisense fragment revealed after doxycycline induction reduced expression of endogeneous elF-4AI mRNA correlated with decreased proliferation rates (up to 6%). These data demonstrate the applicability of antisense strategies against translation factors in melanoma cells. Translation initiation factor elF-4AI contributes to the control of melanoma cell proliferation and may be taken into consideration when scheduling new therapeutic approaches targeting the translational control. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index