Expression of peroxisome proliferator-activated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists.
Peroxisome proliferator-activated receptor (PPAR) gamma is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPARgamma activation induces growth inhibition in these cells. PPARgamma expression in human gastric cancer cells, however, has not been fully investigated. We report the PPARgamma expression in human gastric cancer, and the effect of PPARgamma ligands on proliferation of gastric carcinoma cell lines. Immunohistochemistry was used to demonstrate the presence of PPARgamma protein in surgically resected specimens from well differentiated, moderately differentiated and poorly differentiated adenocarcinoma. We used reverse transcription-polymerase chain reaction and Northern and Western blot analyses to demonstrate PPARgamma expression in four human gastric cancer cell lines. PPARgamma agonists (troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J2) showed dose-dependent inhibitory effects on the proliferation of the gastric cancer cells, and their effect was augmented by the simultaneous addition of 9- cis retinoic acid, a ligand of RXRalpha. Flow cytometry demonstrated G1 cell cycle arrest and a significant increase of annexin V-positive cells after treatment with troglitazone. These results suggest that induction of apoptosis together with G1 cell cycle arrest may be one of the mechanisms of the antiproliferative effect of PPARgamma activation in human gastric cancer cells.
Sato
H
H
Second Department of Internal Medicine, Shimane Medical University, Izumo, Shimane, Japan.
Ishihara
S
S
Kawashima
K
K
Moriyama
N
N
Suetsugu
H
H
Kazumori
H
H
Okuyama
T
T
Rumi
M A
MA
Fukuda
R
R
Nagasue
N
N
Kinoshita
Y
Y
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000819:agonists* / Q000096:biosynthesis*; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C105492:9,13-retinoic acid; D014212:Tretinoin