Effects of proteasome inhibitors on expression of activating transcription factor-4 of undifferentiated thyroid cancer cells

OBJECTIVE:To investigate the role of activating transcription factor(ATF)-4 in thyroid cancer cell death induced by proteasome inhibitors.METHODS:The undifferentiated thyroidcancer FRO cells were treated with vehicle,proteasome inhibitor MG132;ATF-4 expression levels were knockdown by RNA interference;ATF-4 and 150×103 oxygen-regulated protein(ORP150) mRNA and protein levels were analyzed by using real time RT-PCR and Western blot,respectively;the apoptotic rate was analyzed by using flow cytometry(FCM).RESULTS:MG132 significantly increased the mRNA and protein levels of ATF-4(P0.01) in undifferentiated thyroid cancer FRO cells;small interfering RNA against ATF-4(si ATF-4) markedly reduced the ATF-4 and ORP150 mRNA and protein levels when compared to vehicle or scramble siRNA(P0.01),in addition siATF-4 dramatically increased MG132 mediated increase in apoptotic cells(P0.01).CONCLUSION:Proteasome inhibitors increase the ATF-4 expression in undifferentiated thyroid cancer FRO cells and the suppression of ATF-4 and ORP150 expression by siATF-4 significantly enhances the apoptosis of FRO cells induced by proteasome inhibitors.