Radis s on SAS Royal H ote l Be rge n , Norw ay

Mitogen–activated protein(MAP) kinase path-ways play critical roles in the pathogenesis of variousmalignancies. The protein kinase Raf–1 constitutive ac-tivation have been identified in a range of human tumors,including acute myelogenous leukemia(AML). The col-lective evidence suggests that Raf–1 is a viable anticancerdrug target. We therefore targeted Raf–1 downstream ofRas using Bay 43–9006 that inhibit Raf–1 kinase activ-ity. Experiments were carried out to determine the roleof Bay 43–9006 in gene expression differentiation bycDNAmicroarray comprising 19200 genes. In this study,gene expression profiling after drug treatment were com-pared to pretreatment. Expression analysis showed thatthere is no huge difference after 3–day treatment, somegenes expression which is commonly associated with cel-lular proliferation and apoptosis were suppressed, such asKMO, RAD51 and CCND1, Raf–1 was enhanced in re-sponder, but slightly down regulated in non–responder,which is associated with Bay 43–9006 resistance. Invitro experiment also showed Bay 43–9006 induced sub-