However, during cancer development, cells frequently lose their response to TGF-β growth inhibitory activity, either through mutations in TGF-β signaling mediators, such as TGF-β receptor type II (TβRII), Smad2 and Smad4 [13], or through alterations in cell cycle regulatory proteins, viz., down-regulation of p53, p21 and pRb [14] or up-regulation of Myc, Akt, Ras/ERK1/2 (extracellular signal regulated kinase 1/2) [13]. This evidence concerns the gene MAPK3 and cancer.