alitretinoin and Carcinoma--Transitional-Cell

alitretinoin has been researched along with Carcinoma--Transitional-Cell* in 1 studies

Other Studies

1 other study(ies) available for alitretinoin and Carcinoma--Transitional-Cell

Article	Year
Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death. Neoplasia (New York, N.Y.), 1999, Volume: 1, Issue:4 The present study examined the expression and role of the thiazolidinedione (TZD)-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma), in human bladder cancers. In situ hybridization shows that PPARgamma mRNA is highly expressed in all human transitional epithelial cell cancers (TCCa's) studied (n=11). PPARgamma was also expressed in five TCCa cell lines as determined by RNase protection assays and immunoblot. Retinoid X receptor alpha (RXRalpha), a 9-cis-retinoic acid stimulated (9-cis-RA) heterodimeric partner of PPARgamma, was also co-expressed in all TCCa tissues and cell lines. Treatment of the T24 bladder cancer cells with the TZD PPARgamma agonist troglitazone, dramatically inhibited 3H-thymidine incorporation and induced cell death. Addition of the RXRalpha ligands, 9-cis-RA or LG100268, sensitized T24 bladder cancer cells to the lethal effect of troglitazone and two other PPAR- activators, ciglitazone and 15-deoxy-delta(12,14)-PGJ2 (15dPGJ(2)). Troglitazone treatment increased expression of two cyclin-dependent kinase inhibitors, p21(WAF1/CIP1) and p16(INK4), and reduced cyclin D1 expression, consistent with G1 arrest. Troglitazone also induced an endogenous PPARgamma target gene in T24 cells, adipocyte-type fatty acid binding protein (A-FABP), the expression of which correlates with bladder cancer differentiation. In situ hybridization shows that A-FABP expression is localized to normal uroepithelial cells as well as some TCCa's. Taken together, these results demonstrate that PPARgamma is expressed in human TCCa where it may play a role in regulating TCCa differentiation and survival, thereby providing a potential target for therapy of uroepithelial cancers. Topics: Alitretinoin; Antineoplastic Agents; Apoptosis; Carcinoma, Transitional Cell; Carrier Proteins; Cell Death; Chromans; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA; DNA, Complementary; Dose-Response Relationship, Drug; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; G1 Phase; Humans; Immunoblotting; In Situ Hybridization; Ligands; Luciferases; Myelin P2 Protein; Neoplasm Proteins; Nicotinic Acids; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; Ribonucleases; Tetrahydronaphthalenes; Thiazoles; Thiazolidinediones; Transcription Factors; Transcriptional Activation; Transfection; Tretinoin; Troglitazone; Tumor Cells, Cultured; Tumor Suppressor Proteins; Urinary Bladder Neoplasms	1999

Article

Year

Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death.

Neoplasia (New York, N.Y.), 1999, Volume: 1, Issue:4

The present study examined the expression and role of the thiazolidinedione (TZD)-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma), in human bladder cancers. In situ hybridization shows that PPARgamma mRNA is highly expressed in all human transitional epithelial cell cancers (TCCa's) studied (n=11). PPARgamma was also expressed in five TCCa cell lines as determined by RNase protection assays and immunoblot. Retinoid X receptor alpha (RXRalpha), a 9-cis-retinoic acid stimulated (9-cis-RA) heterodimeric partner of PPARgamma, was also co-expressed in all TCCa tissues and cell lines. Treatment of the T24 bladder cancer cells with the TZD PPARgamma agonist troglitazone, dramatically inhibited 3H-thymidine incorporation and induced cell death. Addition of the RXRalpha ligands, 9-cis-RA or LG100268, sensitized T24 bladder cancer cells to the lethal effect of troglitazone and two other PPAR- activators, ciglitazone and 15-deoxy-delta(12,14)-PGJ2 (15dPGJ(2)). Troglitazone treatment increased expression of two cyclin-dependent kinase inhibitors, p21(WAF1/CIP1) and p16(INK4), and reduced cyclin D1 expression, consistent with G1 arrest. Troglitazone also induced an endogenous PPARgamma target gene in T24 cells, adipocyte-type fatty acid binding protein (A-FABP), the expression of which correlates with bladder cancer differentiation. In situ hybridization shows that A-FABP expression is localized to normal uroepithelial cells as well as some TCCa's. Taken together, these results demonstrate that PPARgamma is expressed in human TCCa where it may play a role in regulating TCCa differentiation and survival, thereby providing a potential target for therapy of uroepithelial cancers.

Topics: Alitretinoin; Antineoplastic Agents; Apoptosis; Carcinoma, Transitional Cell; Carrier Proteins; Cell Death; Chromans; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA; DNA, Complementary; Dose-Response Relationship, Drug; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; G1 Phase; Humans; Immunoblotting; In Situ Hybridization; Ligands; Luciferases; Myelin P2 Protein; Neoplasm Proteins; Nicotinic Acids; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; Ribonucleases; Tetrahydronaphthalenes; Thiazoles; Thiazolidinediones; Transcription Factors; Transcriptional Activation; Transfection; Tretinoin; Troglitazone; Tumor Cells, Cultured; Tumor Suppressor Proteins; Urinary Bladder Neoplasms

1999