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The ras pathway Is often mutated and Is a strong oncogene that contrIbutes to many malIgnancIes.To assess the role of each ras Isoform, mefs defIcIent In ras(All or In dIfferent combInatIons)Are analyzed In regard of prolIferatIon, mIgratIon, cell cycle, and downstream proteIn effects.The scIentIst careful and clear InVestIgatIons proVided followIng conclusIons: (I)Ras is essential for proliferation and migration,(Ii)Deletion of all isoforms leads a to static state, but not to apoptosis or senescence,(Iii)All ras forms initiate proliferation, but kras is most potent,(IV)Rafmapk is the main downstream signaling inflicting proliferation,(V)Craf activates the stress response through ink4a activation,(Vi)Pi3k and ralgef are not essential for proliferation however, they support rafinflicted proliferation,(Vii)Ras increases cdk4 and cyclind1 activity but not through increased expression of cyclind1,(Viii)Inactivation of the pocket proteins or knock down of prb relieved mefs from their outlet milano hogan dependence on ras signaling to proliferate.
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