Silencing of ATF2 inhibits growth of pancreatic cancer cells and enhances sensitivity to chemotherapy.
Pancreatic cancer is one of the leading causes of cancer-related death worldwide. Activating transcription factor 2 (ATF2) is a multifunctional transcription factor, and is implicated in tumor progress, yet its role in pancreatic cancer remains unclear. In the present study, the level of ATF2 in pancreatic cancer tissues and the adjacent non-tumorous tissues was detected by quantitative real-time PCR and Western blot. The roles of ATF2 in the proliferation, cell cycle, and apoptosis of pancreatic cancer cells were investigated through ATF2 silencing, and the effect of ATF2 shRNA on the sensitivity of pancreatic cancer cells to gemcitabine, an anti-tumor drug, was explored. The results of our study showed that the ATF2 level in the pancreatic cancer tissues was higher than that in the adjacent non-tumorous tissues. Silencing of ATF2 was found to inhibit proliferation, arrest cell cycle at G1 phase and induce apoptosis in pancreatic cancer cells. Moreover, ATF2 silencing enhanced gemcitabine-induced growth-inhibition and apoptosis-induction effects in pancreatic cancer cells. In summary, silencing of ATF2 inhibited the growth of pancreatic cancer cells and enhanced the anti-tumor effects of gemcitabine, suggesting that ATF2 plays a pro-survival role in pancreatic cancer. Our results also propose that a high level of ATF2 may serve as a potential biomarker of pancreatic cancer, and that ATF2 may become a potential target for anti-tumor therapy.
Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Mu
M
Li
Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Xingda
X
Wu
Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Ning
N
Liu
Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Xiaoying
X
Li
Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Fanbin
F
Meng
Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Shaowei
S
Song
D051698:Activating Transcription Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D000093542:Gemcitabine
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D000093542:Gemcitabine
ATF2; apoptosis; cell cycle; drug-resistance; growth; pancreatic cancer