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-rasval12 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-rasAsn17 dominant-negative mutant gene resulted in reduced Fas-L expression. Transfection of the Ha-rasAsn17 into glioma cells also inhibited the activation of NFKB, which is a downstream component of Ras signaling. Accordingly, the membrane-permeable NFKB 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 3-D-thiogalactoside. In summary, these results suggest that the enhanced Ras signaling with consequential NFKB activation, which is a frequent defect found in tumors, could mediate the Fas-L expression of tumors.
Yang
B C
BC
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. y1357@mail.ncku.edu.tw
Wang
Y S
YS
Liu
H S
HS
Lin
S J
SJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism*; D053222:Fas Ligand Protein; D005910:Glioma / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D008148:Lovastatin; D018631:ras Proteins