Ras signaling is involved in the expression of Fas-L in glioma

Fas-L expresses on a variety of tumors and is suspected to modify the dialog between tumor and the immune system. However, the cellular abnormality in tumor cells leading to an aberrant expression of Fas-L is unclear. In this study, we demonstrate the involvement of Ras signaling in the Fas-L expression in several ways. First, the activated Ha-ras(Val12) gene enhanced the Fas-L expression of primary human glial cells. Second, blocking the Ras signal pathway in glioma cells by lovastatin or the Ha-ras(Asn17) dominant- negative mutant gene resulted in reduced Fas-L expression. Transfection of the Ha-ras(Asn17) into glioma cells also inhibited the activation of NFκB, which is a downstream component of Ras signaling. Accordingly, the membrane- permeable NFκB competitor suppressed the Fas-L expression. Furthermore, the Fas-L expression coincided with the Ras activity in the murine 212 cells, in which the Ras activity could be induced by isopropyl β-D-thiogalactoside. In summary, these results suggest that the enhanced Ras signaling with consequential NFκB activation, which is a frequent defect found in tumors, could mediate the Fas-L expression of tumors.