Because the balance between antiapoptotic and proapoptotic proteins is critical to drug-induced apoptosis, we evaluated changes in Bcl-2 family proteins in AZD6244 sensitive and resistant lung cancer cell lines and found that the MEK inhibitor AZD6244 up-regulates the proapoptotic BH3-only proteins Bim, PUMA and NOXA, a process associated with subsequent cell death. The gene discussed is PMAIP1; the disease is lung cancer.