Angiotensin II type 1 receptor expression in human pancreatic cancer and growth inhibition by angiotensin II type 1 receptor antagonist.
We investigated the expression of angiotensin II type 1 receptor (AT1) in pancreatic cancer. Both AT1 mRNA and protein were expressed in human pancreatic cancer tissues and cell lines. Binding assays showed that pancreatic cancer cells have specific binding sites for angiotensin II and that binding could be eliminated by treatment with a selective AT1 antagonist in a dose-dependent fashion. Surprisingly, the growth of cancer cells was significantly suppressed by treatment with antagonist, also in a dose-dependent manner. These observations suggest AT1 plays an important role in pancreatic cancer growth. Furthermore, ligand-induced inhibition of AT1 may be a useful therapeutic strategy.
Fujimoto
Y
Y
First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
Sasaki
T
T
Tsuchida
A
A
Chayama
K
K
D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809