Angiotensin II activates MAP kinase and NF-kappaB through angiotensin II type I receptor in human pancreatic cancer cells.
Pancreatic ductal cancer has higher angiotensin II concentrations compared with normal pancreas or other solid tumors. This study examined angiotensin II type 1 (AT1) receptor expression and the role of angiotensin II in proliferation and survival of human pancreatic cancer cells. All three pancreatic cancer cell lines studied, from well to poorly-differentiated types, HPAF-II, AsPC-1, and Panc-1, showed strong expression of AT1 receptor. In contrast, HT-29 human colon cancer cells showed extremely weak expression. Angiotensin II stimulated the growth of pancreatic cancer cells through MAP kinase activation but had no significant effect on proliferation of HT-29 colon cancer cells. In addition, angiotensin II significantly prevented cisplatin (CDDP)-induced apoptosis through NF-kappaB activation and the subsequent production of anti-apoptotic molecules, including survivin and Bcl-XL, in pancreatic cancer cells. These findings suggest that angiotensin II plays a role in the growth and chemoresistance of AT1-positive pancreatic cancer cells through its action as a potent mitogen and anti-apoptotic molecule.
Amaya
Koji
K
Department of Gastroenterologic Surgery, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, Japan.
Ohta
Tetsuo
T
Kitagawa
Hirohisa
H
Kayahara
Masato
M
Takamura
Hiroyuki
H
Fujimura
Takashi
T
Nishimura
Gen-Ichi
G
Shimizu
Koichi
K
Miwa
Koichi
K
D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D015398:Signal Transduction; D000077022:Survivin; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D044140:Receptor, Angiotensin, Type 1; D000077022:Survivin; D051020:bcl-X Protein; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases