Peroxisome proliferator-activated receptor (PPAR) immunocytochemical expression was analyzed in seven human bladder tumor cell lines (TCCSUP, RT112, VMCUB1, 639V, T24, RT4, SG65), which were also injected in nude mice to assess their tumorigenicity and metastatic ability. PPARα expression was moderate (1.84-5.38% of positive cells) in all cell lines, except for SG65 (11.53%). PPARβ/δ expression was weak (1.50-3.18%) in RT112, TCCSUP, T24, 639V, and greater (5.90-7.77%) in VMCUB1, RT4, SG65. PPARγ expression was low (2.19-3.61%) in not tumorigenic cells (TCCSUP, RT112); it was the highest (10.06- 14.54%) in cells causing tumors resembling human papillary superficial bladder cancers (639V, VMCUB1); it was high (5.80-7.99%) in cells causing tumors resembling human papillary invasive bladder cancers (RT4, T24); it was the lowest (0.73%) in SG65 cells, inducing tumors resembling human solid invasive bladder cancers. These results, confirmed by western blotting, indicate a negative association between PPARγ expression and malignancy in bladder cancer cells. To evaluate the significance of this negative association, the in vitro apoptotic effect of 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), a natural PPARγligand, and of ciglitazone (CGT), a synthetic PPARγ ligand, on four human bladder tumor cell lines (TCCSUP, 639V, T24, SG65), exhibiting different levels of PPARγ expression and representative of different in vivo behaviors, was investigated. While the apoptotic effect of CGT became evident after 48 h and was higher in not tumorigenic (TCCSUP) than in tumorigenic (639V, T24, SG65) cells, the apoptotic effect of 15d-PGJ2 appeared earlier, after 24 h, and was higher in high PPARγ expressing cells causing well differentiated papillary tumors (639V, T24) and lower in low PPARγ expressing cells either not tumorigenic (TCCSUP) or causing undifferentiated malignant cancers (SG65). Since 15d-PGJ2 is abundantly present in human urine, its apoptotic effect could explain the low malignancy and the slow progression of most papillary bladder cancers expressing high levels of PPARγ.
EXPRESSION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN HUMAN BLADDER CANCER CELL LINES AND CORRELATION WITH TUMORIGENICITY AND MALIGNANCY
CALZA, Roberta;FERRI, Albertino
2005
Abstract
Peroxisome proliferator-activated receptor (PPAR) immunocytochemical expression was analyzed in seven human bladder tumor cell lines (TCCSUP, RT112, VMCUB1, 639V, T24, RT4, SG65), which were also injected in nude mice to assess their tumorigenicity and metastatic ability. PPARα expression was moderate (1.84-5.38% of positive cells) in all cell lines, except for SG65 (11.53%). PPARβ/δ expression was weak (1.50-3.18%) in RT112, TCCSUP, T24, 639V, and greater (5.90-7.77%) in VMCUB1, RT4, SG65. PPARγ expression was low (2.19-3.61%) in not tumorigenic cells (TCCSUP, RT112); it was the highest (10.06- 14.54%) in cells causing tumors resembling human papillary superficial bladder cancers (639V, VMCUB1); it was high (5.80-7.99%) in cells causing tumors resembling human papillary invasive bladder cancers (RT4, T24); it was the lowest (0.73%) in SG65 cells, inducing tumors resembling human solid invasive bladder cancers. These results, confirmed by western blotting, indicate a negative association between PPARγ expression and malignancy in bladder cancer cells. To evaluate the significance of this negative association, the in vitro apoptotic effect of 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), a natural PPARγligand, and of ciglitazone (CGT), a synthetic PPARγ ligand, on four human bladder tumor cell lines (TCCSUP, 639V, T24, SG65), exhibiting different levels of PPARγ expression and representative of different in vivo behaviors, was investigated. While the apoptotic effect of CGT became evident after 48 h and was higher in not tumorigenic (TCCSUP) than in tumorigenic (639V, T24, SG65) cells, the apoptotic effect of 15d-PGJ2 appeared earlier, after 24 h, and was higher in high PPARγ expressing cells causing well differentiated papillary tumors (639V, T24) and lower in low PPARγ expressing cells either not tumorigenic (TCCSUP) or causing undifferentiated malignant cancers (SG65). Since 15d-PGJ2 is abundantly present in human urine, its apoptotic effect could explain the low malignancy and the slow progression of most papillary bladder cancers expressing high levels of PPARγ.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
