Gene alterations by peroxisome proliferator-activated receptor gamma agonists in human colorectal cancer cells.
The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear transcription factor that controls the genes involved in metabolism and carcinogenesis. In the present study, we examined the alteration of gene expression in HCT-116 human colorectal cancer cells by PPARgamma agonists: MCC-555 (5 microM), rosiglitazone (5 microM), and 15-deoxy-Delta12,14-prostaglandin J2 (1 microM). The long-oligo microarray data revealed a list of target genes commonly induced (307 genes) and repressed (32 genes) by tested PPARgamma agonists. These genes were analyzed by Onto-Express software and KEGG pathway analysis and revealed that PPARgamma agonists are involved in cell proliferation, focal adhesion, and several signaling pathways. Eight genes were selected to confirm the microarray data by RT-PCR and real-time PCR, from which CSTA, DAP13, TAF12, RIS1, CDKN3 and MAGOH were up-regulated, and KLHL11 and NCOA2 were down-regulated. This study elucidates the commonly induced genes modulated by tested PPARgamma ligands involved in the different signaling pathways and metabolisms, probably mediated in a PPARgamma-dependent manner in colorectal cancer cells and helps to better understand the pleiotropic actions of PPARgamma ligands.
Cekanova
Maria
M
Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996, USA.
Yuan
Joshua S
JS
Li
Xiuoon
X
Kim
Kyubo
K
Baek
Seung Joon
SJ
D015179:Colorectal Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D047495:PPAR gamma / Q000819:agonists* / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D015533:Transcriptional Activation
C477819:15-deoxyprostaglandin J2; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015230:Prostaglandin D2